Myocardial injury in patients with acute ischemic stroke detected by cardiovascular magnetic resonance imaging.

BACKGROUND: Patients with acute ischemic stroke (AIS) are at high risk of adverse cardiovascular events. Until now, the burden of myocardial injury derived from cardiovascular magnetic resonance imaging (CMR) has not been established in this population. METHODS: Patients with AIS underwent CMR at 3 Tesla within 120 h after the index stroke as part of a prospective, single-center study. Patients with persistent atrial fibrillation were excluded. Morphology and function of both cardiac chambers and atria were assessed applying SSFP cine. Myocardial tissue differentiation was based on native and contrast-enhanced imaging including late gadolinium enhancement (LGE) after 0.15 mmol/kg gadobutrol for focal fibrosis and parametric T2- and T1-mapping for diffuse findings. To detect myocardial deformation global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain was measured applying feature tracking. Cardiac troponin was measured using a high-sensitivity assay (99th percentile upper reference limit 14 ng/L). T2 mapping values were compared with 20 healthy volunteers. RESULTS: CMR with contrast media was successfully performed in 92 of 115 patients (mean age 74 years, 40% female, known myocardial infarction 6%). Focal myocardial fibrosis (LGE) was detected in 31 of 92 patients (34%) of whom 23/31 (74%) showed an ischemic pattern. Patients with LGE were more likely to have diabetes, prior myocardial infarction, prior ischemic stroke, and to have elevated troponin levels compared to those without. Presence of LGE was accompanied by diffuse fibrosis (increased T1 native values) even in remote cardiac areas as well as reduced global radial, circumferential and longitudinal strain values. In 14/31 (45%) of all patients with LGE increased T2-mapping values were detectable. CONCLUSIONS: More than one-third of patients with AIS have evidence of focal myocardial fibrosis on CMR. Nearly half of these changes may have acute or subacute onset. These findings are accompanied by diffuse myocardial changes and reduced myocardial deformation. Further studies, ideally with serial CMR measurements during follow-up, are required to establish the impact of these findings on long-term prognosis after AIS.

Selected Metabolic Markers in Girls with Turner Syndrome: A Pilot Study.

BACKGROUND: Turner syndrome (TS) predisposes an individual to obesity and related metabolic disorders. As the TS population is at a higher risk of cardiovascular diseases and malformations, research into laboratory markers of metabolic complications has been ongoing. Special significance has recently been attributed to matrix metalloproteinases (MMPs), their inhibitors (TIMPs), and neurotrophic factors, such as BDNF and GDNF. OBJECTIVE: To establish whether cardiometabolic risk in patients with TS is reflected in the concentrations of metalloproteinases and neurotrophic factors. METHOD: The concentrations of circulating MMP-1, MMP-2, MMP-9, TIMP-1, BDNF, GDNF, and VEGF were measured in 17 patients with TS. The control group was composed of 11 girls with nonpathologic short stature and normal karyotype. RESULTS: There were no differences in chronological or bone age. No significant differences were observed in mean weight, although the Z-score BMI was higher in the study group. The mean baseline values of MMP-1 and BDNF were significantly lower in the control group than in the study group (p < 0.001, p = 0.001). Regression analysis revealed a positive correlation between MMP-1 concentrations and Z-score BMI (r = 0.36, p = 0.047) and between BDNF and Z-score BMI (r = 0.48, p = 0.013). CONCLUSION: Our pilot study showed that MMP-1 may be a potential indicator of a higher risk of cardiometabolic complications in girls with TS. The elevated concentrations of BDNF in normal-weight girls with TS need to be studied further, taking into consideration the influence of estrogen-androgen imbalance.

Status of cathelicidin IL-37, cytokine TNF, and vitamin D in patients with pulmonary tuberculosis.

Development of Mycobacterium tuberculosis (Mtb) infection depends on the ability of the host to elicit the protective immune response to the pathogen. Cathelicidin plays a role in antibacterial innate immunity mechanisms. This peptide contributes to the barrier function of respiratory epithelium and takes part in controlling pulmonary bacterial infections. LL-37 (leucine-leucine-37) is involved in host defense and innate immune response to mycobacterial infections, as well. This study aims to evaluate the serum concentrations of LL-37 in individuals with active pulmonary tuberculosis (TB) and to determine whether any correlations between peptide LL-37, tumor necrosis factor (TNF) and vitamin D serum levels exist. A total of 46 adults with pulmonary TB were recruited for the study. Sixty-one controls were randomly selected as control group. Serum concentrations of cathelicidin LL-37, vitamin D (25(OH)D), as well as TNF, were measured using an enzyme-linked immunosorbent assay (ELISA) kit. The mean (± SEM) level of LL-37 was significantly higher in the TB group (7.45±1.58) compared with healthy controls (1.41±0.22) (p less than 0.001). Mean serum concentration of TNF was significantly higher in the TB group (8.51±1.92) compared with healthy controls (2.69±0.19) (p less than 0.001). There was no significant difference in mean serum levels of vitamin D between healthy (26.10±1.74) and TB subjects (24.18±1.95). No correlations between LL-37, TNF, and vitamin D levels in patients with TB were observed. Our results indicated that serum levels of peptide LL-37 during TB is raised significantly, and this observation is compatible with the general view of the important role of this cathelicidin in defense mechanisms against Mtb infection.

Mast cells participate in chronic low-grade inflammation within adipose tissue.

Obesity is reckoned as one of the civilization diseases, posing a considerable global health issue. Evidence points towards a contribution of multitude immune cell populations in obesity pathomechanism and the development of chronic low-grade inflammation in the expanded adipose tissue. Notably, adipose tissue is a reservoir of mast cells which number in individuals with obesity particularly increased. Some of them tend to degranulation what generate secretion of strong pro-inflammatory and regulatory mediators, as well as cytokines/chemokines. Several lines of evidence suggest that mast cells are strictly associated with pro-inflammatory status in adipose tissue by their indirect impact on immune cell attraction and activation. Furthermore, mast cells affect adipose tissue remodelling and fibrosis by adipocyte differentiation, fibroblast proliferation and enhancing extracellular matrix proteins expression. This review will summarize current knowledge on mast cell features and their role in the development of chronic low-grade inflammation within adipose tissue.

Serum level of cathelicidin LL-37 in patients with active tuberculosis and other infectious diseases.

A growing body of evidence indicates the role of cathelicidin LL-37, a member of the antimicrobial peptide family, in host innate defense mechanisms. The important role of this peptide in infectious diseases is also suggested, however, to date, data relating to LL-37 expression in the course of bacterial infections are far from complete. Therefore, the aim of the present study was to determine LL-37 serum levels in adult patients with pulmonary tuberculosis (TB). For comparison, circulating LL-37 levels in patients with pneumonia induced by Gram-positive or Gram-negative bacteria species and in healthy subjects were evaluated. Fifty patients with pulmonary TB, 31 patients with pneumonia caused by gram-positive bacteria, 68 individuals with pneumonia caused by Gram-negative bacteria, and 61 randomly selected healthy subjects were enrolled in the study. Serum LL-37 concentration was measured using an enzyme-linked immunosorbent assay (ELISA). We established that the mean level of LL-37 was statistically significantly higher in TB patients than that in patients with Gram-positive bacteria-induced pneumonia (p < 0.001), in patients with Gram-negative bacteria-induced pneumonia (p < 0.001), and in healthy controls (p < 0.001). In patients with TB, no statistically significant correlations between serum LL-37 and CRP concentrations (r = -0.2042; p = 0.189) and between serum LL-37 concentration and WBC count (r = -0.1277; p = 0.414) were observed. Our observations clearly documented that cathelicidin LL-37 plays a role in defense mechanisms against infectious agents, and is particularly important when the infection is caused by an intracellular pathogen.

Mast cells generate cysteinyl leukotrienes and interferon-beta as well as evince impaired IgE-dependent degranulation upon TLR7 engagement.

Mast cells are numerous at anatomical sites close to external environment, virtually at the portals of infection. A few data indicated that these cells express cytoplasmic Toll-like receptors (TLRs) recognizing virus-derived molecules. Accordingly, mast cells could participate in anti-viral defense or/and in viral-related diseases. However, data concerning the influence of viruses on mast cell activity are limited. Thus, the aim of our study was to determine mast cell response to TLR7 ligand, i.e. resiquimod (R848), a synthetic mimic of viral ssRNA. Since mast cells play a central role in allergic reactions the effect of TLR7 agonist was also investigated on FcepsilonRI-dependent mast cell response. Experiments were carried out in vitro on freshly isolated fully mature rat peritoneal mast cells. Mast cells exhibit constitutive TLR7 molecule expression and its up-regulation after the agonist challenge. TLR7-mediated mast cell stimulation resulted in cysteinyl leukotriene (cysLT) and interferon (IFN)-beta synthesis, whereas no histamine and CXCL8 secretion was stated. Moreover, mast cell priming with TLR7 ligand caused the reduction in anti-IgE-induced histamine release. The results suggest that ssRNA viruses could directly activate mast cells to alter their phenotype and to release of potent proinflammatory mediators or indirectly modulate IgE-dependent allergic processes.

Mycobacterium tuberculosis CwsA interacts with CrgA and Wag31, and the CrgA-CwsA complex is involved in peptidoglycan synthesis and cell shape determination.

Bacterial cell division and cell wall synthesis are highly coordinated processes involving multiple proteins. Here, we show that Rv0008c, a novel small membrane protein from Mycobacterium tuberculosis, localizes to the poles and on membranes and shows an overall punctate localization throughout the cell. Furthermore, Rv0008c interacts with two proteins, CrgA and Wag31, implicated in peptidoglycan (PG) synthesis in mycobacteria. Deletion of the Rv0008c homolog in M. smegmatis, MSMEG_0023, caused bulged cell poles, formation of rounded cells, and defects in polar localization of Wag31 and cell wall synthesis, with cell wall synthesis measured by the incorporation of the [(14)C]N-acetylglucosamine cell wall precursor. The M. smegmatis MSMEG_0023 crgA double mutant strain showed severe defects in growth, viability, cell wall synthesis, cell shape, and the localization of the FtsZ, FtsI, and Wag31 proteins. The double mutant strain also exhibited increased autolytic activity in the presence of detergents. Because CrgA and Wag31 proteins interact with FtsI individually, we believe that regulated cell wall synthesis and cell shape maintenance require the concerted actions of the CrgA, Rv0008c, FtsI, and Wag31 proteins. We propose that, together, CrgA and Rv0008c, renamed CwsA for cell wall synthesis and cell shape protein A, play crucial roles in septal and polar PG synthesis and help coordinate these processes with the FtsZ-ring assembly in mycobacteria.

Effect of scaling and root planing on interleukin-1ß, interleukin-8 and MMP-8 levels in gingival crevicular fluid from chronic periodontitis patients.

BACKGROUND AND OBJECTIVE: There are few data concerning the effect of scaling and root planing on the levels of immune and inflammatory mediators in gingival crevicular fluid from patients with chronic periodontitis. Therefore, in this study the influence of scaling and root planing was determined on amounts of interleukin (IL)-1ß, IL-8 and MMP-8 in gingival crevicular fluid from patients with chronic periodontitis, in relation to clinical parameters. MATERIAL AND METHODS: A total of 51 patients were enrolled in this study. The study population consisted of 30 patients with generalized advanced chronic periodontitis, while 21 periodontally healthy subjects were recruited for the control group. The clinical parameters included approximal plaque index, gingival index, pocket depth and clinical attachment loss. The amounts of IL-1ß, IL-8 and MMP-8 in gingival crevicular fluid were measured by ELISA. Periodontal parameters as well as gingival crevicular fluid humoral factor amounts were evaluated in the control group and in chronic periodontitis patients at baseline and at 1 and 4 wk after scaling and root planing treatment. RESULTS: At baseline, there were significant differences between control subjects and chronic periodontitis patients in terms of clinical attachment loss, pocket depth, gingival index (p < 0.001) and approximal plaque index (p < 0.01). The amounts of IL-1ß, MMP-8 (p < 0.001) and IL-8 (p < 0.01) in gingival crevicular fluid were significantly lower in healthy subjects than in chronic periodontitis patients. Scaling and root planing led to improvement in all examined clinical parameters, apart from clinical attachment loss. Periodontal treatment also resulted in a significant decrease in the amounts of IL-1ß, IL-8 and MMP-8 in comparison to baseline, especially 4 wk after scaling and root planing (p < 0.001); however, the amounts of these humoral factors were still higher than those in control group. CONCLUSION: Our observations indicated that short-term nonsurgical therapy resulted in a significant improvement in periodontal indices and in a marked decrease of IL-1ß, IL-8 and MMP-8 gingival crevicular fluid levels. Nevertheless, no significant correlations were found between clinical parameters and amounts of humoral factors after therapy.

Lipopolysaccharide from Porphyromonas gingivalis stimulates rat mast cells to cysteinyl leukotriene generation and upregulates Toll-like receptor -2 and -4 expression.

Mast cells are found in all tissues of the oral cavity and it is suggested that they take part in the development of oral inflammation. As Porhyromonas gingivalis is widely recognized as a major pathogen in the development and progression of gingivitis and periodontitis, the aim of our study is to determine the effect of P. gingivalis lipopolysaccharide (LPS) on mast cell degranulation, cysteinyl leukotriene (cysLT) generation, and migration, as well as Toll-like receptor (TLR)-2 and -4 expression. Experiments were carried out in vitro on rat peritoneal mast cells. LPS-induced mast cell histamine release was estimated by a spectrofluorometric method and cysLT generation by ELISA test. Mast cell migration in response to this antigen was examined according to Boyden's modified method and TLR expression was determined by flow cytometry. We found that P. gingivalis LPS did not induce mast cell degranulation and histamine release. However, activation of mast cells with this bacterial antigen resulted in generation and release of significant amounts of cysLTs. We also documented that LPS from P. gingivalis did not stimulate mast cell migration, even in the presence of laminin, whereas it strongly upregulated TLR2 and TLR4 expression on mast cells. Observations that P. gingivalis LPS activates mast cells to generate and release proinflammatory mediators such as cysLTs and modulates TLR2 and TLR4 expression indicates that these cells might be involved in the emergency of inflammatory processes evolved in response to P gingivalis infection.

Vaginal bacterial flora activates rat peritoneal mast cells.

Sixteen strains of physiological and pathological vaginal bacteria were tested for their ability to secrete histamine from rat peritoneal mast cells in vitro. We noticed that Mycoplasma hominis-induced histamine release was very high (up to 53.6%). The stimulation of rat mast cells with Staphylococccus cohnii, Staphylococcus coagulase(-) (two strains), Ureaplasma urealyticum, Peptostreptococcus spp., Bacteroides capillosus, Staphylococcus aureus and Streptococcus agalactiae resulted in lower but significant histamine secretion (11.2%-17.5%). Other bacteria strains (Staphylococcus epidermidids, Enterococcus faecalis, Escherichia coli, Actinomyces naeslundii (two strains) and Lactobacillus fermentum (two strains) caused very low (4.2% - 8.8%) histamine release.

Computer analysis of normal and basal cell carcinoma mast cells.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequently observed neoplasm of the human skin. Mast cells are regarded as important cellular elements of all organs and tissues of the human body. They are involved in many physiological and pathological processes, including inflammation and fibrotic changes observed in BCC. The aim of our study was to characterise in detail mast cells observed in BCC and normal skin on the basis of computer analysis techniques. MATERIAL AND METHODS: Series of photographs obtained from histopathological biopsies of basal cell carcinomas from 18 patients, stained specifically for mast cells with Astra blue and nuclear red, were employed for the study. Control group consisted of series of photographs from normal skin obtained from 18 persons who underwent plastic surgery operations. All the photographs underwent digital computer analysis by means of a number of subroutines written in Delphi developed at the Technical University of Lódz. RESULTS: Specific staining allowed for thresholding the image and subsequently mast cells were visualised as black objects on a white background. Those objects were then analysed in detail i.e. their geometrical features (area, perimeter, maximal diameter) were calculated. The employed image analysis techniques allowed for the differentiation and detailed characteristics of mast cells stained with Astra blue and nuclear red. CONCLUSIONS: We observed that mast cells in BCC gathered mainly in fibrous stroma and were more numerous, had considerably larger area, longer perimeter and maximal diameter than normal skin mast cells.

Can the 1,5-disubstituted tetrazole ring modify the co-ordinating ability and biological activity of opiate-like peptides?

The copper(II) complexing ability and the biological activity of beta-casomorphin-7 tetrazole analogues have been investigated. Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies have been used to establish the thermodynamic stability, speciation and structure of Cu(II) complexes with YP-psi(CN4)-FPGPI-NH2 (1), YPF-psi(CN4)-AGPI-NH2 (2) and YPFP-psi(CN4)-GPI-NH2 (3). Comparison of the binding ability of the tetrazole analogues reveals that the most effective ligand for copper(II) is YPF-psi(CN4)-AGPI-NH2. The effectiveness of this ligand comes from its particular conformation suited for the Cu(II) 2N co-ordination mode in the physiological pH region. The ability of casomorphin tetrazole analogues to activate rat mast cells to histamine release in vitro in the presence of copper(II) has been studied.

The action of tumor necrosis factor-alpha on rat mast cells.

Taking into account that cytokine tumor necrosis factor-alpha (TNF-alpha) and mast cells (MC) both are involved in inflammation, it seems of great importance to recognize their relationships. Therefore, we have studied whether recombinant human TNF-alpha (rHuTNF-alpha) can cause histamine secretion from rat peritoneal MC. We have also examined the effect of this cytokine on MC reactivity. We have established that TNF-alpha stimulates rat MC to histamine release in a concentration-dependent manner. TNF-alpha-induced histamine secretion was evoked by concentrations > 10-16 M and reached the maximum rate at a concentration of 10-10 M (histamine release 17.1% +/- 1.9%, mean +/- SEM). We have also noticed that pretreatment of MC with TNF-alpha (in a concentration of 10-16 M) significantly inhibited concanavalin A (ConA)-stimulated release of histamine, with the percent release decreasing to 51% of the control value. Treatment of mast cells with TNF-alpha resulted in a decrease of compound 48/80-dependent histamine release as well (the percent released histamine fell to 85% of the control value). This altered MC responsiveness was reversible. After 120 min of resting time, the MC reactivity came back to the initial values. We have concluded that TNF-alpha appears to be a direct stimulus for MC to release histamine, and it may regulate MC secretory function.

[The influence of anaerobic bacteria and mycoplasma isolated from the genital tract on mast cell activation]. / Wplyw bakterii beztlenowych i mykoplazm izolowanych z dróg rodnych kobiet na aktywacje mastocytów szczura.

Nowadays, it is known that mast cells, numerously appearing in all organs and being a source of a wide range of mediators and cytokines, are involved both in physiological and pathological processes. The aim of our study was to examine whether vaginal bacteria, especially those participating in Bacterial vaginosis, are able to activate mast cells to mediators secretion. The study was done on rat peritoneal mast cells. The mast cells were incubated in vitro with suspensions of Bacteroides capillosus, Actinomyces naeslundii (2 strains), Peptostreptococcus spp., Lactobacillus fermentum (2 strains), Mycoplasma hominis or Ureaplasma urealyticum killed by temperature. Activation of mast cells was estimated on the basis of histamine release. It was established that M. hominis, U. urealyticum and B. capillosus strongly stimulated rat mast cells to histamine secretion (histamine release 53.0%, 17.4% and 10.0%, respectively). Histamine release induced by Peptostreptococcus spp., A. naeslundii and L. fermentum was lower (at a range of 2.4%-8.2%). The obtained results can suggest that presumably interactions between vaginal bacteria and placental mast cells could influence the course of pregnancy.

Intestinal mucosa-associated bacteria modulate rat mast cell reactivity.

It is well known that in some conditions bacteria of physiological flora of gastrointestinal tract may become pathogenic. Each complaint which causes injury of gastrointestinal wall integrity permits bacteria to penetrate the tissues and affect the tissue cells. Since mast cells represent one of very important and numerous cellular elements of the gastrointestinal tract walls, bacteria can exert the effects on them. Therefore, the aim of our study was to examine the influence of four strains of intestinal mucosa-associated bacteria--Bacteroides thetaiotaomicron, Bacteroides fragilis, Bifidobacterium adolescentis and Escherichia coli on the mast cell reactivity. Our experiments were performed in vitro on isolated rat peritoneal mast cells and the reactivity of these cells was estimated on the basis of histamine release. We used the suspensions of whole bacteria, killed by heating at 65 degrees C. We have noticed that the magnitude of bacteria-induced histamine release from mast cells was very low (up to 6.0%) when compared with histamine release induced with Con A, compound 48/80 and TNF-alpha. However, all studied bacteria changed the reactivity of mast cells in anaphylactic (with ConA) and anaphylactoid (with compound 48/80) reactions. After 40 min preincubation with B. thetaioataomicron, B. fragilis, B. adolescentis or E. coli ConA-induced histamine release was diminished up to 25%, 71%, 58% and and 68% of maximal histamine release, respectively. Preincubation of rat mast cells with B. thetaioataomicron, B. fragilis, B. adolescentis or E. coli also changed their reactivity in anaphylactoid reaction with compound 48/80 (histamine release was diminished up to 70%, 63%, 63% and 60%, respectively).

Tumor necrosis factor alpha (TNF-alpha) modulates rat mast cell reactivity.

Nowadays there is growing evidence that some cytokines regulate biological functions of the mature mast cells. Therefore, we have studied whether TNF-alpha, the cytokine of multifunctional activities, could directly stimulate rat peritoneal mast cells to histamine secretion and whether it could modulate rat mast cell reactivity in anaphylactic (with ConA) and anaphylactoid (with compound 48/80) reactions. We have established that rat recombinant TNF-alpha does not activate rat mast cells to histamine release. However, TNF-alpha-treatment causes the decrease of spontaneous histamine release up to 85% (TNF-alpha concentration: 2 x 10(-9) M). Pretreatment of mast cells with TNF-alpha inhibits ConA-stimulate release of histamine with the percent release decreasing up to 33.7% of the control value (TNF-alpha concentration: 5 x 10(-9) M) and this decrease is statistically significant. Pretreatment of mast cells with TNF-alpha reduces compound 48/80-dependent histamine release as well and the percent release of histamine fell to 64.7% of the control value. We have concluded that TNF-alpha may play a significant role in regulation of mast cell secretory activity.

[Mastocyte proteinase]. / Proteinazy mastocytów.

Recent studies have led to a rapid expansion of knowledge concerning the structure and biology of mast cells neutral proteinases. Therefore, in this paper tryptases, chymases, carboxypeptidases and cathepsin G have been described and their biological roles have been discussed.

In vitro reactivity of mast cells in urticaria pigmentosa skin.

The aim of our study was to evaluate the sensitivity of skin mast cells from urticaria pigmentosa (UP) patients to substance P (SP), tumor necrosis factor alpha (TNF-alpha) and anti-IgE, and to compare the sensitivity of these cells with that of skin mast cells from healthy human donors. Mast cells for in vitro functional studies were obtained using an enzymatic dispersion technique from skin biopsies (from 11 patients with UP and 11 healthy donors), and the reactivity of these cells was estimated on the basis of histamine release. Our observations indicated that UP skin mast cells and healthy skin mast cells had similar sensitivities to challenge with TNF-alpha at a concentration 10(-7) M (16.4% vs 15.2%) and with anti-IgE at a dilution 1:100 (41.0% vs 37.0%). However, UP mast cells showed considerably higher sensitivity to challenge with SP at a concentration 10(-4) M than healthy skin mast cells (20.0% vs 6.8%), and the difference was statistically significant (P < 0.001). UP skin mast cells also demonstrated significantly higher spontaneous histamine release than healthy skin mast cells (32.1% vs 12.4%, P < 0.001). Our findings indicating UP skin mast cell sensitivity to SP might suggest that mechanisms involving neurogenic inflammation could contribute to the course of this disease.

Functional studies of skin mast cells in lichen planus.

In order to identify possible functional differences between mast cells obtained from the skin of lichen planus (LP) patients and healthy donors, biopsies from lesional skin of 11 lichen planus patients and from normal skin of 7 healthy donors were sampled. Mast cells were obtained from the skin using an enzymatic dispersion technique. The cells were challenged in vitro with substance P (SP), tumor necrosis factor alpha (TNF-alpha) and anti-IgE. Their reactivity was estimated on the basis of histamine release. LP skin mast cells and healthy skin mast cells showed similar sensitivity to stimulation with TNF-alpha at a concentration of 10(-7) M (15.2% histamine release, as a proportion of total cellular content vs 15.9%) and to stimulation with anti-IgE at a dilution of 1:100) (38.8% vs 37.0%). Spontaneous histamine release was also very similar in both the populations of mast cells (10.2% vs 12.7%, respectively). However, LP skin mast cells showed significantly higher (P < 0.01) sensitivity towards stimulation with SP at a concentration of 10(-4) M than healthy skin mast cells (15.9% histamine release vs 7.0%). This finding could suggest that neurogenic inflammatory mechanisms contribute to the pathogenesis of LP.

Sensitivity of human cutaneous mast cells to anaphylactic and nonimmunological stimuli.

Mast cells represent significant cellular element of the skin. It is now postulated that they play an important role in cutaneous homeostasis and are engaged in some pathological processes as well. The aim of our study was to examine sensitivity of human cutaneous mast cells to anaphylactic and anaphylactoid stimuli. The studies were performed on human cutaneous mast cells obtained from healthy skin by enzymatic dispersion technique. The mast cells were activated in vitro with anti-IgE, concanavalin A (Con A), compound 48/80, substance P (SP) or tumor necrosis factor alpha (TNF-alpha). We have noticed that skin mast cells were susceptible to the challenge with anti-IgE and Con A, and histamine release was dose- and time-dependent. In both cases histamine release was high (44.0 +/- 4.1% with anti-IgE at dilution 1:500 and 20.1 +/- 2.4% with Con A in concentration 500 micrograms/ml). Cutaneous mast cells were challenged in a dose- and time-related fashion with compound 48/80, however histamine release was low (9.8 +/- 2.4%, at concentration of compound 48/80-100 micrograms/ml). SP and TNF-alpha also activated mast cells but the magnitude of histamine release was not high (up to 7.1 +/- 0.9%, SP in concentration 10(-4) M and 17.4 +/- 1.1%, TNF-alpha in concentration 10(-6) M) and maximal after 20 min reaction.