Luschka and the carotid body / Luschka e o corpo carotídeo

The 'carotid body' is a small structure sited at the bifurcation of the common carotid artery. The macroscopic features of the carotid body, and items of the extrinsic nervous, and vascular supplies, were initially described by Taube (1743), complemented by a number of authors that followed, proceeding until Luschka (1962), who added the first microscopic study. The macroscopic features of the carotid body, including location, extrinsic innervation, and vascular supply, then provided, were described in a relatively satisfactory manner. However, despite Luschka's great and admirable effort, the microscopic findings seem to be flawed, what can be ascribed to the technical limitations at the time, and the artifacts due to the used procedures. Nevertheless, there is no doubt that Luschka and his forerunners provided an important step for forthcoming research on the carotid body, and its innervation.

O 'corpo carotídeo' é uma pequena estrutura situada na bifurcação da artéria carótida comum. Os aspectos macroscópicos do corpo carotídeo e itens sobre o suprimento nervoso e vascular extrínsecos foram descritos inicialmente por Taube (1743), complementados por um certo número de autores que seguiram, prosseguindo até Luschka (1962), que acrescentou o primeiro estudo microscópico. Os aspectos macroscópicos do corpo carotídeo, incluindo localização, inervação extrínseca e suprimento vascular, então providos, foram descritos de modo relativamente satisfatório. Entretanto, apesar do grande e admirável esforço de Luschka, os achados microscópicos aparecem falhos, o que pode ser atribuído às limitações técnicas daquele tempo e a artefatos devidos aos procedimentos utilizados. Todavia, não há dúvida que Luschka e seus precursores proveram um importante passo para pesquisas que vieram sobre o corpo carotídeo e da sua inervação.

Insights into the signal transduction pathways of mouse lung type II cells revealed by transcription factor profiling in the transcriptome

Alveolar type II cells constitute a small fraction of the total lung cell mass. However, they play an important role in many cellular processes including trans-differentiation into type I cells as well as repair of lung injury in response to toxic chemicals and respiratory pathogens. Transcription factors are the regulatory proteins dynamically modulating DNA structure and gene expression. Transcription factor profiling in microarray datasets revealed that several members of AP1, ATF, NF-kB, and C/EBP families involved in diverse responses were expressed in mouse lung type II cells. A transcriptional factor signature consisting of Cebpa, Srebf1, Stat3, Klf5, and Elf3 was identified in lung type II cells, Sox9+ pluripotent lung stem cells as well as in mouse lung development. Identification of the transcription factor profile in mouse lung type II cells will serve as a useful resource and facilitate the integrated analysis of signal transduction pathways and specific gene targets in a variety of physiological conditions.

Characterization of air-liquid interface culture of A549 alveolar epithelial cells

Alveolar epithelia play an essential role in maintaining the integrity and homeostasis of lungs, in which alveolar epithelial type II cells (AECII) are a cell type with stem cell potential for epithelial injury repair and regeneration. However, mechanisms behind the physiological and pathological roles of alveolar epithelia in human lungs remain largely unknown, partially owing to the difficulty of isolation and culture of primary human AECII cells. In the present study, we aimed to characterize alveolar epithelia generated from A549 lung adenocarcinoma cells that were cultured in an air-liquid interface (ALI) state. Morphological analysis demonstrated that A549 cells could reconstitute epithelial layers in ALI cultures as evaluated by histochemistry staining and electronic microscopy. Immunofluorescent staining further revealed an expression of alveolar epithelial type I cell (AECI) markers aquaporin-5 protein (AQP-5), and AECII cell marker surfactant protein C (SPC) in subpopulations of ALI cultured cells. Importantly, molecular analysis further revealed the expression of AQP-5, SPC, thyroid transcription factor-1, zonula occludens-1 and Mucin 5B in A549 ALI cultures as determined by both immunoblotting and quantitative RT-PCR assay. These results suggest that the ALI culture of A549 cells can partially mimic the property of alveolar epithelia, which may be a feasible and alternative model for investigating roles and mechanisms of alveolar epithelia in vitro.

The role of alveolar type II cells in swine leptospirosis / O papel das células alveolares tipo II na leptospirose suína

This study aimed to investigate a possible relationship between alveolar type II cells and the inflammatory response to infection with Leptospira spp., and thus comprise a further element that can be involved in the pathogenesis of lung injury in naturally infected pigs. The study group consisted of 73 adult pigs that were extensively reared and slaughtered in Teresina, Piauí state, and Timon, Maranhão state, Brazil. The diagnosis of leptospirosis was made using the microscopic agglutination test (MAT) aided by immunohistochemistry and polymerase chain reaction. The MAT registered the occurrence of anti-Leptospira antibodies in 10.96% (8/73) of the pigs. Immunohistochemistry allowed for the visualization of the Leptospira spp. antigen in the lungs of 87.67% (64/73) of the pigs. There was hyperplasia of bronchus-associated lymphoid tissue and circulatory changes, such as congestion of alveolar septa, parenchymal hemorrhage and edema within the alveoli. Lung inflammation was more intense (p = 0.0312) in infected animals, which also showed increased thickening of the alveolar septa (p = 0.0006). Evaluation of alveolar type II (ATII) cells using an anti-TTF-1 (Thyroid Transcription Factor-1) antibody showed that there were more immunostained cells in the non-infected pigs (53.8%) than in the infected animals (46.2%) and that there was an inverse correlation between TTF-1 positive cells and the inflammatory infiltrate. There was no amplification of Leptospira DNA in the lung samples, but leptospiral DNA amplification was observed in the kidneys. The results of this study showed that a relationship exists between a decrease in alveolar type II cells and a leptospire infection. Thus, this work points to the importance of studying the ATII cells as a potential marker of the level of lung innate immune response during leptospirosis in pigs...

Setenta e três suínos adultos de criação extensiva, abatidos em Teresina, no estado do Piauí e Timon, no estado do Maranhão, constituíram o grupo de estudo. O diagnóstico da leptospirose foi realizado utilizando a técnica de soroaglutinação microscópica (MAT), auxiliada por imunoistoquímica e reação em cadeia pela polimerase. A SAM registrou a ocorrência de anticorpos anti-leptospiras em 10,96% (8/73) dos suínos. A imunoistoquímica permitiu a visualização de antígenos de Leptospira spp. em pulmões de 87,67% (64/73) dos suínos. Havia hiperplasia do tecido linfoide associado ao brônquio e alterações circulatórias como, congestão do septo alveolar, hemorragia parenquimatosa e edema no interior de alvéolos. Os focos de inflamações pulmonares eram mais numerosos (p=0,0312) nos animais infectados, bem como o espessamento do septo alveolar (p=0,0006). A quantificação de células alveolares tipo II marcadas pelo anticorpo anti-TTF-1 (Thyroid Transcription Factor-1) mostrou que existia mais células imunocoradas em suínos não infectados (53,8%) comparados aos infectados (46,2%) e uma correlação inversa em relação ao infiltrado inflamatório. Não houve amplificação de DNA de Leptospira spp. em amostras de tecido pulmonar, no entanto DNA leptospiral foi observado em rim. Os resultados deste estudo mostraram que existe uma relação entre a diminuição das células alveolares tipo II e a infecção por leptospiras. Dessa forma, este trabalho aponta para a importância do estudo dessas células, como um provável marcador da modulação da resposta imune inata do pulmão na leptospirose em suínos...

Influence of Yiwei Huayu Powder on immune drift in patients with precancerous lesions of gastric cancer / 中草药

Objective: To observe the curative effect of Yiwei Huayu Powder (YHP) and the expression of Th1/Th2 cytokines in patients with precancerous lesions of gastric cancer (PLGC). Methods: There were 100 diagnosed chronic atrophic gastritis (CAG) with gastric mucous membrane dysplasia (Dys) and/or intestinal metaplasia (IM) patients who were randomly divided into treatment group (50 cases) and control group (50 cases). The patients in the treatment group were administrated with YHP for three months, while the other one with Teprenone Capsules and folic acid. Results: Compared with the control group, the symptom scores of the patients in the treatment group decreased more obviously (P < 0.05). Compared with the control group, the pathological scores of the patients in the treatment group decreased more obviously (P < 0.05). After the treatment, the expression of the Th1 (IL-2, INF-γ) level escalated and the Th2 (IL-4, IL-6) level decreased in the treatment group, which existed an obvious difference compared to the control group (P < 0.05). Conclusion: YHP has played a therapeutic effect in patients with PLGC through intervening immune drift and inducing tumor cell apoptosis, thereby blocking or reversing the development of PLGC.

Effect of Short-term Exposure of Different Concentrations of Hyperoxia on Fetal Alveolar Type II Cell Death

PURPOSE: Lung injury imposed by hyperoxia is the most important cause of bronchopulmonary dysplasia (BPD) in premature lungs, and hyperoxia has the chief biological effect of inducing cell death. The objective of this study was to investigate the response of cell death in fetal alveolar type II cells (FATIICs) exposed to different concentrations of hyperoxia for 36 h. METHODS: FATIICs were isolated on embryonic day 19 and exposed to 65%- or 85%-oxygen for 36 h. Cells in room air were used as controls. FACScan was performed in hyperoxic and control samples at 0/6/12/24/36 h, and the patterns of cell death were compared at each time point using flow-cytometry. RESULTS: Cell necrosis as measured by selective propidium iodide staining increased significantly from 12 h of 65%-hyperoxia and 6 h of 85%-hyperoxia, respectively. Cell necrosis increased 1.6-fold, 3.0-fold and 4.6-fold after 12 h, 24 h, and 36 h, respectively during 65%-hyperoxia and increased by 2.4-fold, 3.1-fold, 6.3-fold, and 8.8-fold after 6 h, 12 h, 24 h, and 36 h, respectively during 85%-hyperoxia compared to controls. Apoptotic cells as measured by selective Annexin-V staining peaked at 1.3% at 24 h of 65%-hyperoxia and peaked at 1.2% at 6 h of 85%-hyperoxia, respectively and then decreased rapidly. CONCLUSION: This study shows that exposure to sublethal and lethal hyperoxia increases necrosis of FATIICs remarkably from the early stage of hyperoxia. These findings support the idea that short-term exposure to oxygen from birth may contribute to the evolution of "new" BPD in preterm lungs.

Interleukin-10 Down-Regulates Cathepsin B Expression in Fetal Rat Alveolar Type II Cells Exposed to Hyperoxia

PURPOSE: Hyperoxia has the chief biological effect of cell death. We have previously reported that cathepsin B (CB) is related to fetal alveolar type II cell (FATIIC) death and pretreatment of recombinant IL-10 (rIL-10) attenuates type II cell death during 65%-hyperoixa. In this study, we investigated what kinds of changes of CB expression are induced in FATIICs at different concentrations of hyperoxia (65%- and 85%-hyperoxia) and whether pretreatment with rIL-10 reduces the expression of CB in FATIICs during hyperoxia. MATERIALS AND METHODS: Isolated embryonic day 19 fetal rat alveolar type II cells were cultured and exposed to 65%- and 85%-hyperoxia for 12 h and 24 h. Cells in room air were used as controls. Cytotoxicity was assessed by lactate dehydrogenase (LDH) released into the supernatant. Expression of CB was analyzed by fluorescence-based assay upon cell lysis and western blotting, and LDH-release was re-analyzed after preincubation of cathepsin B-inhibitor (CBI). IL-10 production was analyzed by ELISA, and LDH-release was re-assessed after preincubation with rIL-10 and CB expression was re-analyzed by western blotting and real-time PCR. RESULTS: LDH-release and CB expression in FATIICs were enhanced significantly in an oxygen-concentration-dependent manner during hyperoxia, whereas caspase-3 was not activated. Preincubation of FATIICs with CBI significantly reduced LDH-release during hyperoxia. IL-10-release decreased in an oxygen-concentration-dependent fashion, and preincubation of the cells with rIL-10 significantly reduced cellular necrosis and expression of CB in FATIICs which were exposed to 65%- and 85%-hyperoxia. CONCLUSION: Our study suggests that CB is enhanced in an oxygen-concentration-dependent manner, and IL-10 has an inhibitory effect on CB expression in FATIICs during hyperoxia.

Fetal Alveolar Type II Cell Injury Induced by Short-term Exposure to Hyperoxia

A High concentration of oxygen (>40%) is used as a life-saving therapy in preterm newborns since birth. By generating excess reactive oxygen species, however, hyperoxia can cause lung injury leading to bronchopulmonary dysplasia (BPD). Although hyperoxia-induced lung injury contributes to the evolution of BPD, the mechanisms by which hyperoxia contributes to the genesis of lung injury in preterm lungs are not yet fully defined, and there are no specific measures for the protection of preterm lungs against injury secondary to hyperoxia. Alveolar type II cells are key components of the alveolar structure, and they are responsible for the restoration of normal alveolar epithelium after acute lung injury. However, hyperoxia is primarily delivered to the alveolar epithelium and alveolar type II cells can be the main target for the injury secondary to hyperoxia. To date, my researches have been focused on injury of fetal alveolar type II cells exposed to hyperoxia and the role of anti-inflammatory cytokine, IL-10 minimizing fetal type II cell injury induced by hyperoxia. Based on my previous studies, this article summarizes the cellular and molecular mechanisms of fetal type II cell injury induced in the early stage of hyperoxia and the protective potency of IL-10 in fetal alveolar type II cells and neonatal lungs injured by hyperoxia.

ANP inhibits surfactant secretion from isoproterenol stimulated alveolar type II cells

In order to investigate the effect of ANP on surfactant secretion from alveolar type II cell(AT II cell) during circulatory derangement in adult respiratory distress syndrome (ARDS), the secretion of surfactant from AT II cells was evaluated in purely isolated AT II cultures from rat lungs. For the simulation of sympathetic stimulation during circulatory derangement, primary AT II cultures were incubated with isoproterenol and IBMX. In this isoproterenol stimulated AT II cells, ANP were added in the media for the investigation of effect of ANP on surfactant secretion from AT II cells. For the evaluation of surfactant secretion,(3H)-methylcholine was incorporated and the level of radiolabelled choline chloride secreted from the cells was determined. As previously reported, isoproterenol and IBMX stimulated surfactant secretion from AT II cells. Isoproterenol showed synergistic increase of surfactant secretion with IBMX in AT II cells. In isoproterenol stimulated AT II cells, physiological level of ANP inhibited the secretion of surfactant in primary cultures of AT II cells. On the basis of these experimental it is suggested that, in association with circulatory change during ARDS, increased secretion of ANP by the pulmonary edema, hypoxia and congestive heart heart failure might aggravate the symptoms of ARDS by reduction of surfactant secretion from AT II cells.

Effects of high dose of dexamethasone on PLA2, GGT activityand lung morphology in NNNMU-induced ARDS rats / 결핵

Background: In order to elucidate one of the pathogenic mechanisms of ARDS associated with pulmonary surfactant and oxidant injury, acute lung injury was induced by N-nitroso- N-methylurethane (NNNMU). In this model, the role of phospholipase A2 (PLA2), surfactant, gamma glutamyl transferase (GGT) and morphology were investigated to delineate one of the pathogenic mechanisms of ARDS by inhibition of PLA2 with high dose of dexamethasone. Method: Acute lung injury was induced in Sprague-Dawley rats by NNNMU which is known to induce acute lung injury in experimental animals. To know the function of the alveolar type II cells, GGT activity in the lung and bronchoalveolar lavage was measured. Surfactant phospholipid was measured also. PLA2 activity was measured to know the role of PLA2 in ARDS. Morphological study was performed to know the effect of PLA2 inhibition on the ultrastructure of the lung by high dose of dexamethasone. Results: Six days after NNNMU treatment (4 mg/kg), conspicuous pulmonary edema was induced and the secretion of pulmonary surfactant was decreased significantly. In the acutely injured rats' lung massive infiltration of leukocytes was observed. At the same time rats given NNNMU had increased PLA2 and GGT activity tremendously. Morphological study revealed bizarre shaped alveolar type II cells and hypertrophied lamellar bodies in the cytoplasm of the alveolar type II cells. But after dexamethasone treatment (20 mg/kg, for six days) in NNNMU-treated rats, these changes were diminished i.e. there were decrease of pulmonary edema and increase of surfactant secretion from alveolar type II cells. Rats given dexamethasone and NNNMU had decreased PLA2 and GGT activity in comparison to NNNMU induced ARDS rats. Conclusion: Inhibition of PLA2 by high dose of dexamethasone decreased pathological findings caused by infiltration of leukocytes and respiratory burst. Based on these experimental results, it is suggested that an activation of PLA2 is the one of the major factors to evoke the acute lung injury in NNNMU-induced ARDS rats.

A STEREOLOGIC ANALYSIS OF LAMELLAR BODY WITHIN PULMONARY ALVEOLAR TYPE Ⅱ CELLS IN DOGS WITH ACUTE HEMORRHAGIC PANCREATITIS / 第二军医大学学报

A stereologic study of lamellar bodies within pulmonary alveolar type II cells in dogs with experimental acute hemorrhagic pancreatitis(group P)and in dogs inje- cted muscularly with choloroquine before inducing pancreatitis (group PI)was carried out.Our findings showed that volumerical density (Vv), surface density (Sv)and numerical density(Nv)of lamellar bodies were decreased by 29.06%,30.28% and 40.75% in the group P as compared with those in the control group (group N), respectively, and their Sv and Nv were decreased by 23.8% and 30.26% in comparison with those in the group PI.The results suggest that the lung injury resulting from acute hemorrhagic pancreatitis was characterized by alveolar surfactant System damage.Dramatical decrease in the number of the lamellar bodies affected the surface tension of alveoli in a certain degree, leading to atelectasis.There was a relationship between lung injury and the effect of PLA2(phospholipidase A2).Choloroquine might play a role in maintaining the number of lamellar bodies.