Association of Surfactant-Associated Protein D Gene Polymorphisms with the Risk of COPD: a Meta-Analysis

The relationship between surfactant-associated protein D polymorphisms and chronic obstructive pulmonary disease risk remains controversial. This article is the first to systematically evaluate this relationship. A comprehensive worldwide search was conducted for relevant literature on surfactant-associated protein D gene mutations and chronic obstructive pulmonary disease risk prediction. Study quality was evaluated using the Newcastle-Ottawa scale. After four genetic models (the allele, additive, recessive, and dominant models) were identified, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were applied in this meta-analysis. The meta-analysis included 659 individuals in the case group and 597 in the control group. In the Asian population, none of the four genetic models revealed any significant association between rs2243639 genotype and the risk of chronic obstructive pulmonary disease. In Caucasians, however, the recessive model exhibited significant risk associated with rs2243639. Furthermore, there was a significant association between rs721917 genotype and the risk of chronic obstructive pulmonary disease in the Asian population. In contrast, none of the four gene models revealed any significant risk associated with this gene in the Caucasian population. This meta-analysis suggests that rs2243639 is not related to the risk of chronic obstructive pulmonary disease in the Asian population but is related to this risk in the Caucasian population. Regarding rs721917, the T allele may increase the risk of chronic obstructive pulmonary disease in the Asian population.

Clinical significance of nuclear factor erythroid 2-related factor 2 in patients with chronic obstructive pulmonary disease

BACKGROUND/AIMS: Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD). However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear. METHODS: Patients diagnosed with COPD were recruited from St. Paul’s Hospital, The Catholic University of Korea, between July 2009 and May 2012. Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30). Seventeen patients were enrolled as a control group (n = 17). The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured. We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters. RESULTS: Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs. COPD-stable vs. COPD-exacerbation) (p = 0.002, p < 0.001). Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent. Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = –0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = –0.342, p = 0.014). However, CRP level was not correlated with any measured parameter. CONCLUSIONS: Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.

Increased peripheral blood TCD4+ counts and serum SP-D levels in patients with chronic paracoccidioidomycosis, during and after antifungal therapy

BACKGROUND The main clinical forms of paracoccidioidomycosis (PCM) are the acute/subacute form (AF) and the chronic form (CF), and they both display considerable clinical variability. The immune responses of PCM patients, during and after treatment, remain neglected, mainly in the case of CF patients, due to the high prevalence of pulmonary sequelae. OBJECTIVE To evaluate the distribution of whole blood T cell subsets, serum cytokines, and biomarkers of pulmonary fibrosis in PCM patients, according to the clinical form and at different time points, during the antifungal therapy. METHODS Eighty-seven PCM patients, from an endemic area in Brazil, were categorised into groups, according to the clinical form (AF or CF) and the moment of treatment. The peripheral blood T lymphocyte subsets of these patients were analysed using fluorescence-activated cell sorting. The serum levels of cytokines, basic fibroblast growth factor and surfactant protein-D (SP-D) were also analysed. FINDINGS In the CF patients, an expansion of the peripheral blood TCD4+ cells was observed during the treatment, and this persisted even after two years of antifungal treatment. In addition, these patients showed high serum levels of SP-D. CONCLUSION Our findings highlight the immunological changes CF patients undergo, during and after treatment, possibly due to the hypoxia triggered by pulmonary fibrosis and emphysema.

Levels of surfactant proteins A and D in bronchoalveolar lavage fluid of children with pneumonia and their relationships with clinical characteristics / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the levels of pulmonary surfactant proteins A and D (SP-A, SP-D) in bronchoalveolar lavage fluid (BALF) of children with pneumonia, and to explore their relationships with clinical characteristics.</p><p><b>METHODS</b>Thirty-five children with pneumonia were enrolled in this study. Differential cell counts were obtained by Countstar counting board. The levels of SP-A and SP-D in BALF were detected using ELISA.</p><p><b>RESULTS</b>In children with pneumonia, SP-D levels were significantly higher than SP-A levels (P<0.001). SP-D levels were negatively correlated with the neutrophil percentage in BALF (r(s)=-0.5255, P<0.01). SP-D levels in BALF in children with increased blood C-reactive protein levels (>8 mg/L) were significantly lower than in those with a normal level of C-reactive protein (P<0.05). Compared with those in children without wheezing, SP-D levels in children with wheezing were significantly lower (P<0.01). There was no correlation between SP-A levels and clinical characteristics.</p><p><b>CONCLUSIONS</b>SP-D levels in BALF are significantly higher than SP-A levels, and have a certain correlation with clinical characteristics in children with pneumonia. As a protective factor, SP-D plays a more important role than SP-A in regulating the immune and inflammatory responses.</p>

Association of surfactant protein D gene polymorphisms at rs3088308 and rs721917 with susceptibility to silicosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between polymorphisms of surfactant protein D (rs3088308 and rs721917) and the susceptibility to silicosis.</p><p><b>METHODS</b>This case-control study included 125 silicosis patients and 125 individuals exposed to industrial dust but without silicosis (control group), who were strictly matched with the case group for age, gender, work type and cumulative length of dust exposure. The rs3088308 and rs721917 polymorphisms of surfactant protein-D were detected in all the participants using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).</p><p><b>RESULTS</b>The frequencies of T/T, T/A and A/A genotypes of surfactant protein-D rs3088308 locus were 22.2%, 71.2% and 5.6% in the case group, significantly different from the frequencies of 17.6%, 58.4% and 24.0% in the control group, respectively (P<0.05). The frequencies of C/C, C/T and T/T genotypes of rs721917 locus were 17.6%, 56.8% and 25.6% in the case group, similar to the frequencies of 15.2%, 60.0% and 24.8% in the control group, respectively (P>0.05).</p><p><b>CONCLUSION</b>Surfactant protein-D rs3088308 polymorphism is significantly associated with silicosis, and the T allele may be a risk factor for silicosis in individuals exposed to industrial dust.</p>

Dynamic changes in expression of clara cell protein and surfactant protein-D expressions in lung tissues and bronchoalveolar lavage fluid of silica-treated rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes in the expression of clara cell protein (CC16) and surfactant protein D (SP-D) in the lung tissues and bronchoalveolar lavage fluid (BALF) of silica-treated rats.</p><p><b>METHODS</b>Eighty-four Wistar rats were randomly divided into control group (n = 42) and silica group (n = 42). The silica group was subsequently divided into 3, 7, 14, 21, 28, and 60 d subgroups. The silicotic model was made by instilling silica suspension directly through the trachea into rat lungs. At 3, 7, 14, 21, 28, and 60 d after silica instillation, 8 rats in each group were sacrificed and their lung tissues and BALF were collected. The expression of SP-D and CC16 in lung tissues was detected by immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of SP-D and CCl6 in BALF.</p><p><b>RESULTS</b>The immunohistochemical assay indicated that CCl6 and SP-D were expressed in lung cells. The ELISA found that in 7, 14, 21, 28, and 60 d silica subgroups, the content of CCl6 in rat BALF was 8.14±0.70, 7.15±0.66, 7.00±0.69, 6.34 ± 0.59, and 5.27±0.49 ng/L, respectively; CCl6 expression decreased gradually with the silica exposure time prolonged, indicating a negative correlation (ra = -0.953, P < 0.01). Compared with the control group, all silica subgroups had significantly decreased CCl6 levels (P < 0.05). The content of SP-D in BALF was 12.20 ± 1.57, 14.41 ± 0.65, and 12.18 ± 0.74 ng/L, respectively, in the 7, 14, and 21 d silica subgroups, significantly higher than that in the control group (P < 0.05).</p><p><b>CONCLUSION</b>The dynamic changes in SP-D and CCl6 protein levels in the lung tissues and BALF of rats could be induced by silica exposure and are related to silica exposure time. With the extension of silica exposure, CCl6 levels are gradually reduced, while the SP-D levels first increase and then fall.</p>

Determination and clinical significance of serum surfactant proteins A and D in children with bronchiolitis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the variation and clinical significance of serum levels of surfactant proteins A (SP-A) and D (SP-D) among children with different degrees of bronchiolitis.</p><p><b>METHODS</b>Seventy children with bronchiolitis were divided into acute (n=42) and recovery phase groups (n=28). According to the severity of symptoms, the acute phase group was further divided into severe (n=12) and mild subgroups (n=30). Another 26 children who were hospitalized in the same period due to non-infectious diseases and had not undergone surgery were used as the control group. Competitive enzyme-linked immunosorbent assay was performed to measure serum levels of SP-A and SP-D in each group.</p><p><b>RESULTS</b>The acute phase group had significantly higher serum levels of SP-A and SP-D compared with the recovery phase (P<0.01) and control groups (P<0.01). Compared with the control group, the recovery phase group had elevated levels of SP-A and SP-D (P<0.01). Within the acute phase group, serum levels of SP-A and SP-D in the severe subgroup were significantly higher than in the mild subgroup (P<0.01).</p><p><b>CONCLUSIONS</b>Serum levels of SP-A and SP-D are significantly elevated in children with acute bronchiolitis, and severe cases have higher serum levels of SP-A and SP-D than mild cases. Even after the relief of clinical symptoms, serum levels of SP-A and SP-D remain high. These findings suggest that serum levels of SP-A and SP-D might be useful biomarkers for evaluating the severity of bronchiolitis among children.</p>

Subclinical interstitial lung damage in workers exposed to indium compounds

OBJECTIVES: The present study was designed to determine whether there is a relationship between indium compound exposure and interstitial lung damage in workers employed at indium tin oxide manufacturing and reclaiming factories in Korea. METHODS: In 2012, we conducted a study for the prevention of indium induced lung damage in Korea and identified 78 workers who had serum indium or Krebs von den Lungen-6 (KL-6) levels that were higher than the reference values set in Japan (3 microg/L and 500 U/mL, respectively). Thirty-four of the 78 workers underwent chest high-resolution computed tomography (HRCT), and their data were used for statistical analysis. RESULTS: Geometric means (geometric standard deviations) for serum indium, KL-6, and surfactant protein D (SP-D) were 10.9 (6.65) microg/L, 859.0 (1.85) U/mL, and 179.27 (1.81) ng/mL, respectively. HRCT showed intralobular interstitial thickening in 9 workers. A dose-response trend was statistically significant for blood KL-6 levels. All workers who had indium levels > or =50 microg/L had KL-6 levels that exceeded the reference values. However, dose-response trends for blood SP-D levels, KL-6 levels, SP-D levels, and interstitial changes on the HRCT scans were not significantly different. CONCLUSIONS: Our findings suggest that interstitial lung changes could be present in workers with indium exposure. Further studies are required and health risk information regarding indium exposure should be communicated to workers and employers in industries where indium compounds are used to prevent indium induced lung damage in Korea.

Increased serum surfactant protein-D in the infants with acute respiratory syncytial virus bronchiolitis

PURPOSE: Collectin family is an important component of innate immunity, of which surfactant protein (SP)-D and mannose-binding lectin (MBL) are the most characterized. We examined SP-D and MBL in young children with acute respiratory syncytial virus (RSV) bronchiolitis. METHODS: Sixty-three children (7 days of hospital stay. All children were evaluated if they had recurrent wheezing during follow-up. SP-D and MBL were measured using enzyme-linked immunosorbent assay in serum collected on admission and compared with controls. Their levels were evaluated in relation to the symptom severity during admission and recurrence of wheezing after discharge. RESULTS: Serum SP-D increased significantly in the patients (P<0.01), but MBL showed no difference compared to the controls. SP-D levels were significantly higher in severe group compared with nonsevere group (P<0.05). SP-D levels in the patients with recurrent wheezing after discharge were significantly higher than in those without (P<0.05). MBL showed no difference in relation to the symptom severity or recurrence of wheezing. CONCLUSION: Our study showed that serum SP-D was associated with the severity of RSV bronchiolitis and suggests that it might be a biomarker of lung injury and recurrence of wheezing illnesses in the young children admitted with their first RSV bronchiolitis.

Expression and significance of pulmonary surfactant protein D and IL-16 in allergic rhinitis and nasal polyps / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To detect the expression and distribution of the lung surfactant protein D (surfactant protein D,SP-D ) and IL-16 in nasal mucosa of allergic rhinitis and nasal polyps, and then probe into their significance in the pathology of allergic rhinitis and nasal polyps.@*METHOD@#Fifteen cases of allergic rhinitis, fifteen cases of nasal polyps and fifteen cases of inferior turbinate mucosa were studied to detect the expression of SP-D and IL-16 by immunohistochemistry method.@*RESULT@#The expression of SP-D and IL-16 in allergic rhinitis and nasal polyps were dramatically higher in controls (P 0.05).@*CONCLUSION@#Both normal tissue and diseased tissue express SP-D and IL-16. SP-D is likely to play key roles in the inflammatory reaction process of allergic rhinitis and nasal polyps. IL-16 is an important eosinophil chemokine in the process of allergic rhinitis and nasal polyps,and it can also enhance the local role of eosinophils,thus it can involve in the process of allergic rhinitis and nasal polyps disease.

Alterations of SP-A, SP-D and KL-6 in serum and bronchoalveolar lavage fluid in children with Mycoplasma pneumoniae pneumonia / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the alterations and relationship of surfactant protein (SP)-A, SP-D and KL-6 in serum and bronchoalveolar lavage fluids (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP).</p><p><b>METHOD</b>Self-control method was used for the study on SP-A, SP-D and KL-6 in serum, infected and non-infected BALFs in 32 MMP children with only one side of MPP.</p><p><b>RESULT</b>The contents of SP-A, SP-D and KL-6 in infected BALF were [mg/L;M (IQR) ]: 243 (90-468) , 187 (43-333) , 148 (47-426) ;104 (37-257) , 56 (25-131) , 35 (12-147) in non-infected BALF; 35 (25-69) , 33 (9-149) and 24 (15-62) in serum. The correlation coefficient of KL-6 between serum and infected BALF were -0.534 and -0.378 (P < 0.05).</p><p><b>CONCLUSION</b>There were significant correlation between the alterations of SP-A, SP-D and KL-6 in serum and lung infection in children with CAP. KL-6 in serum may be more sensitive than SP-A and SP-D.</p>

Nonoxynol-9 berberine plural gel has little effect on expression of SLPI, SP-D and lactoferrin in mice's vagina

The most frequently used spermicide Nonoxynol-9 [N-9] in the clinic alters the vaginal flora, which will result in an increased risk of opportunistic infection. So development of a novel spermicidal and microbicidal drug appears to be inevitable. Vaginal local immune is an important part of vaginal flora. Secretory leukocyte protease inhibitor [SLPI], surfactant proteins D [SP-D], and lactoferrin [LF] are anti-microbial molecules with important roles in immune system of female vaginas. To observe effect of a vaginal spermicide nonoxynol-9 [N-9] berberine plural gel on the expression of SLPI SP-D and LF in mice's vaginas. Female BABL/C mice were randomly divided into following 5 groups: normal control group, blank gel group, berberine gel group, 12% N-9 gel group and N-9 berberine plural gel group. Estradiol benzoate at physiological dose was done by hypodermic injection to every group's mice. After 72h, drug gels were separately injected into the mice's vaginas, while immunohistochemistry and Western blot were taken to detect the expression of the 3 indexes in mice's vaginas respectively after 24h and 72h of gel injection. The differences in the three indexes between normal control group and blank gel group were not significant statistically [p>0.05]. The expression of the three indexes in 12% N-9 gel group was decreased compared to that in blank gel group [p<0.05]. The differences in the three indexes between N-9 berberine plural gel group and blank gel group were not significant statistically [p>0.05]. Also, the three index's level of 24h and 72h in sub observation groups after treatment were without statistical significance [p>0.05]. Application of N-9 berberine plural gel had little impact on antimicrobial peptides in normal mice's vaginas

Surface-bound myeloperoxidase is a ligand for recognition of late apoptotic neutrophils by human lung surfactant proteins A and D

Surfactant proteins A (SP-A) and D (SP-D), both members of the collectin family, play a well established role in apoptotic cell recognition and clearance. Recent in vitro data show that SP-A and SP-D interact with apoptotic neutrophils in a distinct manner. SP-A and SP-D bind in a Ca(2+)-dependent manner to viable and early apoptotic neutrophils whereas the much greater interaction with late apoptotic neutrophils is Ca(2+)-independent. Cell surface molecules on the apoptotic target cells responsible for these interactions had not been identified and this study was done to find candidate target molecules. Myeloperoxidase (MPO), a specific intracellular defense molecule of neutrophils that becomes exposed on the outside of the cell upon apoptosis, was identified by affinity purification, mass-spectrometry and western blotting as a novel binding molecule for SP-A and SP-D. To confirm its role in recognition, it was shown that purified immobilised MPO binds SP-A and SP-D, and that MPO is surface-exposed on late apoptotic neutrophils. SP-A and SP-D inhibit binding of an anti-MPO monoclonal Ab to late apoptotic cells. Fluorescence microscopy confirmed that anti-MPO mAb and SP-A/SP-D colocalise on late apoptotic neutrophils. Desmoplakin was identified as a further potential ligand for SP-A, and neutrophil defensin as a target for both proteins.

Dynamic changes of surfactant protein-D and Clara cell protein expressions in lung tissue and bronchoalveolar lavage fluid of silica-treated rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes of surfactant protein-D (SP-D) and Clara cell protein (CC16) expressions in lung tissue and bronchoalveolar lavage fluid (BALF) of silica-treated rats.</p><p><b>METHODS</b>80 rats were randomly divided into the control group and the silica group. The silicotic animal model was established by direct tracheal instillation of silica suspension into rat lungs surgically. On 7, 14, 21, 28 and 60 d after establishment of the animal model, eight rats in each group were sacrificed and lung tissue and BALF were collected. Lung tissue chip microarray was made in different time points after the silica was injected. Expressions of SP-D and CC16 on tissue microarray were detected with immunohistochemistry and quantified by Image-Pro Plus Version 4.5 for Windows(TM); The SP-D and CC16 levels of BALF were detected with western blot and quantified by Quantity One Version 4.6.2.</p><p><b>RESULTS</b>SP-D expressed very little in alveolar type II and Clara cell intracytoplasmic of control group while its expression significantly increased after 7 d in silica group (P < 0.01) and it reached the peak on the 14 d, after this SP-D expression decreased gradually. CC16 was expressed strongly in intracytoplasmic and it expressed little in nucleus of Clara cell by bronchioles of control while it significantly decreased after 7 d in silica group (P < 0.01), and CC16 expression decreased gradually with the exposed silica time, which was correlated negatively among them (r(s) = -0.967, P < 0.01). On 7 d and 28 d, the SP-D levels of BALF in silica group were significantly higher than control (P < 0.01). Furthermore the SP-D levels of BALF on 28 d was significantly elevated than that on 7 d in silica group (P < 0.01). On 7 d and 28 d, the CC16 levels of BALF in silica group were significantly lower than control (P < 0.01). Moreover, CC16 levels of BALF on 28 d was significantly decreased than that on 7 d in silica group (P < 0.01).</p><p><b>CONCLUSION</b>The dynamic changes of SP-D and CC16 protein expressed in lung tissue and bronchoalveolar lavage fluid could be induced by silica exposure and are related with the silica exposure time.</p>

Effect of dexamethasone on the content of pulmonary surfactant protein D in young rats with acute lung injury induced by lipopolysaccharide / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Pulmonary surfactant protein-D (SP-D) is regarded as a valuable biomarker in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This study was to explore the changes of SP-D content in lung tissue following ALI and the effect of dexamethasone (Dex) on the SP-D content in young rats.</p><p><b>METHODS</b>One hundred and forty-four 21-day-old Sprague-Dawley rats were randomly assigned into control, ALI and Dex-treated groups. ALI was induced by intraperitoneal injection of lipopolysaccharide (LPS) (4 mg/kg) in the rats from the ALI and Dex-treated groups. Normal saline was given for the control group. Dex (5 mg/kg) was administered 1 hr after LPS injection in the Dex-treated group. At each time interval of 6, 12, 24, 36, 48 and 72 hrs after LPS injection, eight rats of each group were randomly chosen and sacrificed. Western blot was employed to detect the content of SP-D in lung tissues.</p><p><b>RESULTS</b>The pulmonary SP-D content decreased significantly at 36, 48 and 72 hrs after LPS administration in the ALI group, and reduced to a nadir (0.92 +/-0.11 vs 3.27 +/- 0.52) at 48 hrs compared with that of the control group (P < 0.01). The SP-D content in the Dex-treated group increased significantly at 36,48 and 72 hrs after LPS administration when compared with the ALI group (P < 0.01). A significant difference in the SP-D content between the Dex-treated and the control group was noted only at 72 hrs after LPS administration (P < 0.05).</p><p><b>CONCLUSIONS</b>The SP-D content in lung tissue was reduced following ALI in young rats at the early stage. Early administration of Dex can significantly increase the pulmonary SP-D content.</p>

Changes of Clara cell protein and surfactant protein-D in serum of patients with silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore changes of Clara cell protein (CC16) and surfactant protein-D (SP-D) in the serum of patients with silicosis.</p><p><b>METHOD</b>The concentrations of CC16 and SP-D were measured in the serum by sandwich enzyme-linked immunosorbent assays. The subjects consisted of 30 healthy volunteers and 90 silica-exposed workers including silica-exposed group, the silicosis of suspects group (0(+)) and the silicosis phase I group, 30 subjects each groups.</p><p><b>RESULTS</b>The concentrations of CC16 in the serum was significantly decreased in silica-exposed workers compared to controls (P < 0.01); The concentrations of CC16 in the serum were higher in lifelong nonsmokers than the current smokers in control subjects (P < 0.05), but they were no differences between lifelong nonsmokers and current smokers of 90 silica-exposed workers. Compared with control subjects, the levels of SP-D in the serum of silicosis suspects (0(+)) and silicosis phase I groups were significantly elevated (P < 0.01, respectively), which were also higher than silica-exposed group (P < 0.05 and P < 0.01, respectively), Discriminant equations set by CC16 and SP-D were used in diagnosis of silicosis, and the rate of accuracy in healthy volunteers, the silica-exposed group and the silicosis phase I group were 86.7%, 86.7% and 76.7%, respectively, The total rate of correct classification hit 84.2%.</p><p><b>CONCLUSION</b>The serum CC16 of long-term silica-exposed workers is decreased, and SP-D is increased gradually.</p>

The importance of surfactant on the development of neonatal pulmonary diseases

Pulmonary surfactant is a substance composed of a lipoprotein complex that is essential to pulmonary function. Pulmonary surfactant proteins play an important role in the structure, function, and metabolism of surfactant; 4 specific surfactant proteins have been identified: surfactant proteins-A, surfactant proteins-B, surfactant proteins-C, and surfactant proteins-D. Clinical, epidemiological, and biochemical evidence suggests that the etiology of respiratory distress syndrome is multifactorial with a significant genetic component. There are reports about polymorphisms and mutations on the surfactant protein genes, especially surfactant proteins-B, that may be associated with respiratory distress syndrome, acute respiratory distress syndrome, and congenital alveolar proteinosis. Individual differences regarding respiratory distress syndrome and acute respiratory distress syndrome as well as patient response to therapy might reflect phenotypic diversity due to genetic variation, in part. The study of the differences between the allelic variants of the surfactant protein genes can contribute to the understanding of individual susceptibility to the development of several pulmonary diseases. The identification of the polymorphisms and mutations that are indeed important for the pathogenesis of the diseases related to surfactant protein dysfunction, leading to the possibility of genotyping individuals at increased risk, constitutes a new research field. In the future, findings in these endeavors may enable more effective genetic counseling as well as the development of prophylactic and therapeutic strategies that would provide a real impact on the management of newborns with respiratory distress syndrome and other pulmonary diseases.

O surfactante pulmonar é uma substância composta por um complexo lipoprotéico essencial para a função pulmonar normal. As proteínas do surfactante têm importante papel na estrutura, função e metabolismo do surfactante. São descritas quatro proteínas específicas denominadas surfactante pulmonar-A, surfactante pulmonar-B, surfactante pulmonar-C e surfactante pulmonar-D. Evidências clínicas, epidemiológicas e bioquímicas sugerem que a etiologia da síndrome do desconforto respiratório é multifatorial com um componente genético significativo. Existem na literatura algumas descrições sobre a presença de polimorfismos e mutações em genes dos componentes do surfactante, particularmente no gene da surfactante pulmonar-B, os quais parecem estar associados à síndrome do desconforto respiratório, síndrome da angustia respiratória aguda e proteinose alveolar congênita. Diferenças individuais relacionadas à síndrome do desconforto respiratórioe síndrome da angustia respiratória aguda e à resposta dos pacientes ao tratamento podem refletir diversidade fenotípica, devido, parcialmente, à variação genética. O estudo das diferenças entre as variantes alélicas dos genes das proteínas do surfactante pode ajudar na compreensão das variabilidades individuais na susceptibilidade ao desenvolvimento de várias doenças pulmonares. A determinação de quais polimorfismos e mutações são, de fato, importantes na patogênese das doenças relacionadas à disfunção das proteínas do surfactante e a possibilidade da realização da genotipagem em indivíduos de alto risco constitui um novo campo de pesquisa, que pode permitir, futuramente, um aconselhamento genético mais efetivo, resultando no desenvolvimento de estratégias profiláticas e terapêuticas que representem um impacto real no manejo dos recém-nascidos portadores da síndrome do desconforto respiratório e outras patologias pulmonares.

A Study on the Relationship Between the Morphologic Change and Surfactant Protein (SP)-A and Surfactant Protein (SP)-D Levels in Intratracheal Bleomycin-Induced Pulmonary Fibrosis in White Rats / 대한주산의학회잡지

OBJECTIVE: Surfactant protein (SP)-A and SP-D are involved in host defense mechanism. The author was prompted to perform a study on morphologic change and SP-A, SP-D level of surfactant after pulmonary injury inflicted by intratracheal bleomycin injection. METHODS: Fifteen white adult rats each weighing 250 g (Sprague-Daw ley) were divided into study (receiving bleomycin, n=9) and control groups (n=6). Study group were given a intratracheal injection of belomycin (5 mg/kg). Two groups were grown for five weeks at twenty five degrees Celsius, after which lung tissue were examined for morphologic change and SP-A and SP-D levels were measured using Western blot assay with densitometer. RESULTS: Before the study, the average weight of the study group was 286.69+/-14.54 g, and control was 286.69+/-14.54 g. Five weeks later, the average weight of the study group was 347.31.31+/-60.53 g and control group 352.71+/-16.84 g. However, no statistical significance was noted. On light microscopy, the control group exhibited normal findings while widening of lung interstitium and fibrotic change coupled with more prominent inflammatory cell infiltration were noted in the study group. The SP-A level were 15.34+/-1.52 ODU/microgram in the study group and 7.70+/-2.81 ODU/microgram in the control. SP-D level were 3.53+/-1.46 ODU/microgram and 7.51+/-2.33 ODU/microgram in the study and control groups respectively, there was a statistical significance (p<0.05). CONCLUSION: The morphologic change after pulmonary fibrosis induced by intratracheal bleomycin injection in white rats can be summarized as chronic inflammatory cell infiltration, fibroblast proliferation, deposition of collagen tissues, and lowering of SP-D level were noted. The increase of SP-A level is subject to further study in the future.

Genética molecular del surfactante pulmonar / Molecular genetics in pulmonary surfactant

Se revisan los estudios que han sido publicados recientemente acerca de las características estructurales de las proteínas constituyentes del surfactante pulmonar natural y los genes que las codifican, así como las variaciones polimórficas en ellos y su asociación con patologías pulmonares que se caracterizan por déficit del surfactante pulmonar

Expression of Collectin in the Human Nasal Mucosa / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Collectins (surfactant protein A and D) are proteins with collagen tails and globular lectin domains that appear to play an important role in the first line of host defense in mammalians. However, it is not known if collectins are also present in human nasal mucosa. The purpose of this study was to investigate the expression of collectin proteins in human nasal mucosa and to compare the expressions of SP-A and D mRNA in the normal nasal mucosa and in chronic inflammatory nasal diseases. MATERIALS AND METHOD: Ten chronic rhinosinusitis patients were recruited and ten normal nasal mucosae were used as normal controls. Reverse transcriptase-polymerase chain reaction was performed to detect SP-A and SP-D mRNA. The level of collectin and GAPDH (glyceraldehyde-3-phosphate dehydrogenase) transcripts were semi-quantified with the desitometry. We have characterized the cellular localization of SP-A and SP-D protein using immunohistochemistry. RESULTS: SP-A2/GAPDH mRNA ratio in chronic rhinitis nasal mucosa is greater compared with that in normal nasal mucosa (p<0.05). SP-A protein was expressed in the nasal epithelium and in the epithelial cells of the submucosal glands. SP-D mRNA and protein were not expressed in the nasal mucosa. CONCLUSION: These data provide the first evidence of the presence of collectins in the human nasal mucosa. These results suggested that up-regulation of collectin in chronic rhinosinusitis may be a protective response for the nasal mucosa.