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Results for “lung epithelial cell”

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At least 19 recordsLinked to original sources

PubMed2005

TNF-alpha and IFN-alpha enhance influenza-A-virus-induced chemokine gene expression in human A549 lung epithelial cells.

Lung epithelial cells are the primary cellular targets for respiratory virus pathogens such as influenza and parainfluenza viruses. Here, we have analyzed influenza A, influenza B and Sendai virus-induced chemokine response in human A549 lung epithelial cells. Influenza virus infection resulted in low CCL2/MCP-1, CCL5/RANTES, CXCL8/IL-8 and CXCL10/IP-10 production at late times of infection. However, when cells were pretreated with TNF-alpha or IFN-alpha, influenza-A-virus-induced chemokine production was greatly enhanced. Cytokine pretreatment resulted in enhanced expression of RIG-I, IKKepsilon, interferon regulatory factor (IRF)1, IRF7 and p50 proteins. Most importantly, influenza-A-virus-induced DNA binding of IRF1, IRF3, IRF7 and NF-kappaB onto CXCL10 ISRE and NF-kappaB elements, respectively, was markedly enhanced in cytokine-pretreated cells. Our results suggest that IFN-alpha and TNF-alpha have a significant role in priming epithelial cells for higher cytokine and chemokine production in influenza A virus infection.

Blotting, Northern↗

PubMed2006

Interleukin-31 and oncostatin-M mediate distinct signaling reactions and response patterns in lung epithelial cells.

Lung epithelial cells are primary targets of oncostatin M (OSM) and, to a lower degree, of interleukin (IL)-6 and IL-31, all members of the IL-6 cytokine family. The OSM receptor (OSMR) signals through activation of STAT and mitogen-activated protein kinase pathways to induce genes encoding differentiated cell functions, reduce cell-cell interaction, and suppress cell proliferation. IL-31 functions through the heteromeric IL-31 receptor, which shares with OSMR the OSMRbeta subunit, but does not engage gp130, the common subunit of all other IL-6 cytokine receptors. Because the response of epithelial cells to IL-31 is unknown, the action of IL-31 was characterized in the human alveolar epithelial cell line A549 in which the expression of the ligand-binding IL-31Ralpha subunit was increased. IL-31 initiated signaling that differed from other IL-6 cytokines by the particularly strong recruitment of the STAT3, ERK, JNK, and Akt pathways. IL-31 was highly effective in suppressing proliferation by altering expression of cell cycle proteins, including up-regulation of p27(Kip1) and down-regulation of cyclin B1, CDC2, CDK6, MCM4, and retinoblastoma. A single STAT3 recruitment site (Tyr-721) in the cytoplasmic domain of IL-31Ralpha exerts a dominant function in the entire receptor complex and is critical for gene induction, morphological changes, and growth inhibition. The data suggest that inflammatory and immune reactions involving activated T-cells regulate functions of epithelial cells by IL-6 cytokines through receptor-defined signaling reactions.

Brain Neoplasms↗

PubMed2000

Role of inducible nitric-oxide synthase in regulation of whole-cell current in lung epithelial cells.

Lung inflammation is associated with enhanced expression of proinflammatory cytokines and increased production of nitric oxide (NO) by inducible NO synthase (iNOS). To investigate the possible relationship between cytokine-induced expression of iNOS and epithelial ion channel function, we measured whole-cell current in A549 cells treated with a mixture of cytokines: tumor necrosis factor, interleukin-1 beta, and interferon-gamma for 12 h. Cytokines significantly increased the expression and activity of iNOS, and reduced generation of cGMP in response to stimulation with NO donor S-nitroso-glutathione (GSNO). Patch-clamp studies showed that 100 microM GSNO increased the whole-cell current from 11.2 +/- 1.8 to 19.6 +/- 2.7 pA/pF (n = 16) in control cells, but had no effect in cytokine-treated cells (n = 9). N-(3-(Aminomethyl)benzyl)acetamidine (1400W), a selective inhibitor of iNOS, restored activation of the current by GSNO in cytokine-treated cells, indicating a crucial role for iNOS in this process. Cells treated with cytokines showed increased levels of peroxynitrite (ONOO(-)), compared with the control, or cells that were treated with the cytokines and 1400W or superoxide dismutase/catalase. Treatment of cells with 100 microM ONOO(-) had no effect on the whole-cell current, but in contrast to untreated cells, subsequent application of GSNO did not activate the current. In conclusion, cytokine-induced expression of iNOS affects activation of the whole-cell current via NO/cGMP pathway, likely by increasing the generation of ONOO(-).

Cyclic GMP↗

PubMed2004

Lung epithelial cells and type II pneumocytes of donor origin after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: In the present investigation, we determined whether donor epithelial lung cells might be detected after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Lung-tissue specimens were obtained at autopsy from four female patients, two with male donors, after nonmyeloablative HSCT. Immunohistochemical staining for cytokeratin was used to identify lung epithelial cells. The tissue sections were analyzed for the presence of donor-derived lung epithelial cells with the use of fluorescence in situ hybridization of XY-positive cells. RESULTS: All patients showed almost complete donor chimerism in all cell lineages after HSCT with polymerase chain reaction of minisatellites. In the two positive controls, between 2% and 6% Y-chromosome-positive epithelial lung cells were detected in each section. Surfactant-positive male epithelial cells were also detected, indicating engraftment of type II pneumocytes. In the two negative controls, no Y-chromosome-positive cells were detected. CONCLUSION: Circulating donor stem cells may differentiate into lung epithelial cells after allogeneic HSCT.

Adult↗

PubMed1997

B[a]P-DNA adduct formation and induction of human epithelial lung cell transformation.

In this study we tested the suitability of the human epithelial lung cell line BEAS-2B for in vitro studies of lung carcinogenesis. The human bronchial epithelial lung cell line BEAS-2B, immortalized with an SV-40/Ad-12 hybrid virus construct, was treated for 24 hours with five different concentrations of the lung carcinogen benzo(a)pyrene (B[a]P) to assess the relationship between DNA adduct levels, cell cycle distribution, micronuclei formation (MN), colony forming efficiency (CFE), and anchorage independent growth (AIG). There appeared to be a strong linear correlation between B[a]P concentration and DNA adduct formation, but no difference in cell cycle distribution was observed after incubation with various concentrations of B[a]P. In the incubation range of 4 to 100 nM B[a]P, the number of DNA adducts was linearly correlated with colony formation in AIG and with the number of cells within individual colonies but not the number of colonies in the CFE test. At higher B[a]P concentrations, the clonal expansion of cells in the CFE and the number of colonies in the AIG declined. Also, the number of micronuclei increased with the formation of DNA adducts. It is concluded that after 24 hours of incubation with 100 nM B[a]P, the formation of BPDE-DNA adducts in the human epithelial lung cells BEAS-2B results in maximal induction of cell transformation. Because of this correlation between DNA adduct formation and lung epithelial cell transformation, the BEAS-2B cells seem suitable for in vitro studies on lung carcinogens.

Benzo(a)pyrene↗

PubMed2005

Oxidative stress response results in increased p21WAF1/CIP1 degradation in cystic fibrosis lung epithelial cells.

Lung epithelium in cystic fibrosis (CF) patients is characterized by structural damage and altered repair due to oxidative stress. To gain insight into the oxidative stress-related damage in CF, we studied the effects of hyperoxia in CF and normal lung epithelial cell lines. In response to a 95% O2 exposure, both cell lines exhibited increased reactive oxygen species. Unexpectedly, the cyclin-dependent kinase inhibitor p21WAF1/CIP1 protein was undetectable in CF cells under hyperoxia, contrasting with increased levels of p21WAF1/CIP1 in normal cells. In both cell lines, exposure to hyperoxia led to S-phase arrest. Apoptotic features including nuclear condensation, DNA laddering, Annexin V incorporation, and elevated caspase-3 activity were not readily observed in CF cells in contrast to normal cells. Interestingly, treatment of hyperoxia-exposed CF cells with two proteasome inhibitors, MG132 and lactacystin, restored p21WAF1/CIP1 protein and was associated with an increase of caspase-3 activity. Moreover, transfection of p21WAF1/CIP1 protein in CF cells led to increased caspase-3 activity and was associated with increased apoptotic cell death, specifically under hyperoxia. Taken together, our data suggest that modulating p21WAF1/CIP1 degradation may have the therapeutic potential of reducing lung epithelial damage related to oxidative stress in CF patients.

Acetylcysteine↗

PubMed2006

Evidence that autocrine signaling through Bmpr1a regulates the proliferation, survival and morphogenetic behavior of distal lung epithelial cells.

Lung development requires reciprocal epithelial/mesenchymal interactions, mediated by signaling factors such as Bmps made in both cell populations. To address the role of Bmp signaling in the epithelium, we have exploited the fact that Bmp receptor type Ia (Alk3) is expressed in the epithelium during branching morphogenesis. Deletion of Bmpr1a in the epithelium with an Sftpc-cre transgene leads to dramatic defects in lung development. There is reduced epithelial proliferation, extensive apoptosis, changes in cell morphology and extrusion of cells into the lumen. By E18.5, there are fewer Type II cells than normal, and the lung contains large fluid-filled spaces. If cell death is prevented by making embryos homozygous null for the proapoptotic gene, Bax, the epithelial cells that are rescued can apparently differentiate, but normal morphogenesis is not restored. To determine whether Bmps made by the epithelium can function in an autocrine manner, mesenchyme-free endoderm was cultured in Matrigel with Fgfs. Under these conditions, the mutant epithelium fails to undergo secondary budding. Abnormal development was also seen when Bmp4 was specifically deleted in the epithelium using the Sftpc-cre transgene. Our results support a model in which Bmp signaling primarily regulates the proliferation, survival and morphogenetic behavior of distal lung epithelial cells.

Animals↗

PubMed2000

Expression of proteins coincident with inducible radioprotection in human lung epithelial cells.

Human lung epithelial cells and many other cell lines are hypersensitive to low doses of ionizing radiation (<0.2 Gy). However, above a threshold dose of 0.4-0.6 Gy, an induced radioprotective response is triggered that protects cells at higher radiation doses. At 4 h, when maximal induced radioprotection is seen in these cells after low-dose priming, the two-dimensional gel protein expression pattern in 0.5-Gy-exposed cells is subtly altered, with seven proteins being 2- to 5-fold down-regulated and one being 2-fold up-regulated. They include: (a) the protein kinase C inhibitor 1, or histidine triad nucleotide-binding motif (HINT) protein; (b) substrates for protein kinase C activity including the chloride intracellular channel protein 1; and (c) a cytoskeletal protein degraded during apoptosis. In addition, a lung cancer-specific protein that binds to both telomeres and nascent mRNA molecules is down-regulated, as is interleukin 1alpha. Therefore, at least in human lung epithelial cells, radioprotection may be the result of signaling pathway switching, which results in the removal of damaged cells and the preparation for enhanced general transcription in surviving cells during a period in which cell proliferation is repressed. This combination of events may be cell-type-specific and may have implications for the protection of normal lung tissue during unavoidable radiation exposure such as in radiotherapy.

Dose-Response Relationship, Radiation↗

PubMed2002

Growth of respiratory syncytial virus in mink lung epithelial cells.

Mink lung epithelial cells (Mv-1-Lu) were tested for their ability to support the growth and serial passage of respiratory syncytial virus (RSV) in vitro. Indian isolates of RSV induced distinctive cytopathic effect with typical rounding of cells followed by detachment with more than 50 per cent cells showing bright fluorescence using anti-RSV monoclonal antibodies in immunofluorescence test. Serial passage of RSV was possible in Mv-1-Lu cells without loss of sensitivity of the cells for virus growth. Titration of cell associated virus and virus released in the supernatant indicated that 60 per cent of the virus was released in the supernatant, and 40 per cent remained cell associated. Transmission electron microscopic studies of negatively stained RSV particles and ultra-thin sections of RSV infected Mv-1-Lu cells showed roughly spherical particles with club shaped projections, budding from the cytoplasmic membrane. These results indicate that Mv-1-Lu cell line is suitable for the growth and propagation of RSV.

Animals↗

PubMed2000

Induction of apoptosis by glyoxal in human embryonic lung epithelial cell line L132.

Oxidative stress has been suggested to play a central role in the pathogenesis of lung fibrosis and lung epithelial cell apoptosis is considered to be a key event during fibrogenesis. Studies from various laboratories have indicated that metabolic conditions may initiate oxidative stress, thereby contributing to epithelial cell death. This study was designed to test the hypothesis that glyoxal, an intermediate product in the glycation reaction leading to advanced glycation end products (AGEs), may induce lung epithelial cell apoptosis. We investigated the in vitro effects of glyoxal on fetal human lung epithelial L132 cells. Immunocytochemical analysis of paraffin-embedded cells and fluorescence-activated cell sorter analysis revealed a dose-dependent accumulation of the glycoxidation product (epsilon)N-carboxymethyllysine (CML) in all compartments of the cell. It has been shown that CML modification of proteins may serve as an indicator for oxidative stress. To examine the role of apoptosis in epithelial lung cells we investigated glyoxal-dependent changes in pro- and antiapoptotic mediators bax and activated caspase-3, and galectin-3 and bcl-2, respectively. Increasing concentrations of glyoxal (50 to 400 microM) induced an increase in the number of apoptotic cells. The apoptotic changes were confirmed by transmission electron microscopy. Immunocytochemical analysis of treated cells revealed the presence of other AGEs such as pentosidine as well as products of lipid peroxidation.

Apoptosis↗

PubMed2002

DNA damage in lung epithelial cells isolated from rats exposed to quartz: role of surface reactivity and neutrophilic inflammation.

Respirable quartz has been classified as a human lung carcinogen (IARC, 1997). However, the mechanisms involved in quartz-induced carcinogenesis remain unclear. The aim of the present study was to investigate acute DNA damage in epithelial lung cells from rats exposed to quartz. Since surface reactivity is considered to play a crucial role in the toxicity of quartz, the effect of surface modifying agents polyvinylpyridine-N-oxide (PVNO) and aluminium lactate (AL) was evaluated. Therefore, rats were instilled with quartz (DQ12, 2 mg/rat) or quartz treated with PVNO or AL. After 3 days animals were killed and brochoalveolar lavage (BAL) was performed to evaluate inflammatory cell influx. BAL-fluid levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP) and total protein were used as lung damage markers. Neutrophil activation was assessed by myeloperoxidase (MPO) measurement, and total antioxidant capacity of the BAL-fluid was determined using the TEAC (trolox equivalent antioxidant capacity) assay. Lung epithelial cells were isolated and DNA strand breakage was determined by single cell gel electrophoresis (comet assay). DNA damage was significantly increased in epithelial cells from rats instilled with DQ12, whereas no enhanced DNA strand breakage was observed when quartz was treated with PVNO or AL. Total protein, LDH and TEAC were increased in rats treated with native quartz, and this was inhibited by both coatings. A significant correlation between neutrophil numbers and MPO levels was observed, indicating neutrophil activation. Inhibition of DNA damage by both coatings was paralleled by a reduction of neutrophil influx as well as MPO activity. In this study we provide evidence that modification of the particle surface prevents DNA strand breakage in epithelial lung cells from quartz-exposed rats. Furthermore, the present data show the feasibility of our in vivo model to evaluate the role of inflammation, antioxidant status, and cytotoxicity in particle-induced DNA damage.

Alkaline Phosphatase↗

PubMed2005

Mitochondrial localization of catalase provides optimal protection from H2O2-induced cell death in lung epithelial cells.

Reactive oxygen species (ROS) can cause cell injury and death via mitochondrial-dependent pathways, and supplementation with antioxidants has been shown to ameliorate these processes. The c-Jun NH(2)-terminal kinase (JNK) pathway has been shown to play a critical role in ROS-induced cell death. To determine if targeting catalase (CAT) to the mitochondria provides better protection than cytosolic expression against H(2)O(2)-induced injury, the following two approaches were taken: 1) adenoviral-mediated transduction was performed using cytosolic (CCAT) or mitochondrial (MCAT) CAT cDNAs and 2) stable cell lines were generated overexpressing CAT in mitochondria (n = 3). Cells were exposed to 250 microM H(2)O(2), and cell survival, mitochondrial function, cytochrome c release, and JNK activity were analyzed. Although all viral transduced cells had a transient twofold increase in CAT activity, MCAT cells had significantly higher survival rates, the best mitochondrial function, and lowest JNK activity compared with CCAT and LacZ controls. The improved protection with MCAT was observed in primary type II lung epithelial cells and in transformed lung epithelial cells. In the three stable cell lines, cell survival directly correlated with extent of mitochondrial localization (r = 0.60572, P < 0.05) and not overall CAT activity (r = -0.45501, P < 0.05). Data indicate that targeting of antioxidants directly to the mitochondria is more effective in protecting lung epithelial cells against ROS-induced injury. This has important implications in antioxidant supplementation trials to prevent ROS-induced lung injury in critically ill patients.

Animals↗

PubMed2002

Dissociation of DNA damage and mitochondrial injury caused by hydrogen peroxide in SV-40 transformed lung epithelial cells.

BACKGROUND: Since lung epithelial cells are constantly being exposed to reactive oxygen intermediates (ROIs), the alveolar surface is a major site of oxidative stress, and each cell type may respond differently to oxidative stress. We compared the extent of oxidative DNA damage with that of mitochondrial injury in lung epithelial cells at the single cell level. RESULT: DNA damage and mitochondrial injury were measured after oxidative stress in the SV-40 transformed lung epithelial cell line challenged with hydrogen peroxide (H2O2). Single cell analysis of DNA damage was determined by assessing the number of 8-oxo-2-deoxyguanosine (8-oxo-dG) positive cells, a marker of DNA modification, and the length of a comet tail. Mitochondrial membrane potential, DeltaPsim, was determined using JC-1. A 1 h pulse of H2O2 induced small amounts of apoptosis (3%). 8-oxo-dG-positive cells and the length of the comet tail increased within 1 h of exposure to H2O2. The number of cells with reduced DeltaPsim increased after the addition of H2O2 in a concentration-dependent manner. In spite of a continual loss of DeltaPsim, DNA fragmentation was reduced 2 h after exposure to H2O2. CONCLUSION: The data suggest that SV-40 transformed lung epithelial cells are resistant to oxidative stress, showing that DNA damage can be dissociated from mitochondrial injury.

Journal Article↗

PubMed2001

Significance of proneural basic helix-loop-helix transcription factors in neuroendocrine differentiation of fetal lung epithelial cells and lung carcinoma cells.

In this brief review article, we describe how cell fate determination by which the airway epithelial cells become neuroendocrine or non-neuroendocrine is regulated by a network of basic helix-loop-helix transcription (bHLH) factors in a similar manner to neuronal differentiation, and how this system could work to determine cell differentiation of human lung carcinomas. Immunohistochemical studies reveal that mammalina achaete-scute complex homologue (Mash)1 is expressed in pulmonary neuroendocrine cells (PNEC), while hairy and Enhancer of split (Hes)1 is expressed in pulmonary non-neuroendocrine cells (non-PNEC). Studies using gene-deficient mice for the bHLH factors revealed that in Mash1 homozygous null mice no PNEC are detected, while PNEC increase markedly in Hes1 homozygous null mice. These observations suggest that Mash1 is an essential positive factor for neuroendocrine differentiation of lung epithelium, and that Hes1 is one of the repressive factors for neuroendocrine differentiation. Moreover, immunohistochemical studies revealed that Notch receptors are detected in non-PNEC, and thus the Notch signalling pathway could play a role in the determination of airway epithelial cell differentiation. In human lung carcinomas, a similar bHLH network should operate to determine cell differentiation phenotypes. Generally, expression of the human homologue of Mash1 (HASH1) is detected in small cell carcinoma and carcinoids, while Hes1 seems to be expressed mainly in non-small cell carcinoma. Thus, proneuronal bHLH factors may play roles in cell fate determination of the airway epithelial system, and may regulate human airway epithelial cells in diseased conditions.

Animals↗

PubMed2005

[Selective heterologous communication among human lung epithelial cells, fibroblasts, and lung cancer PG cells].

OBJECTIVE: To further understand the roles of gap junctional intercellular communication in carcinogenesis and progression of human lung cancer. METHODS: The heterologous communication was characterized among human lung epithelial cells HLEC, human lung fibroblasts HLF, human lung giant carcinoma PG cells and its Cx43 transfectants PG/C4 by using a preloading assay. Cx43 immunofluorescent staining and Northern blot were performed to examine Cx43 gene expression. RESULTS: Although both human lung fibroblasts HLF and epithelial cells HLEC expressed Cx43 and had very strong homologous communication, HLEC cells were unable to communicate with HLF cells. The human lung carcinoma cell line PG was defective of both homologous communication, and heterologous communication with its epithelial origin HLEC. Transfection of Cx43 into PG cells, which rescued PG cells' homologous communication and enhanced heterologous communication with HLF cells, could restore heterologous coupling with HLEC cells. CONCLUSION: Selective heterologous communication exists among different kinds of human lung cells, when human lung carcinoma cells lost coupling with its epithelial origin, Cx43 gene expression is not enough to establish heterologous communication between them.

Cell Communication↗

PubMed1998

Induction of retinoblastoma gene expression during terminal growth arrest of a conditionally immortalized fetal rat lung epithelial cell line and during fetal lung maturation.

The process by which fetal lung epithelial cells differentiate into type 1 and type 2 cell is largely unknown. In order to study lung epithelial cell proliferation and differentiation we have infected 20-day fetal lung epithelial cells with a retrovirus carrying a temperature-sensitive SV40 T antigen (T Ag) and isolated several immortalized fetal epithelial cell lines. Cell line 20-3 has characteristics of lung epithelial cells including the presence of distinct lamellar bodies, tight junctions, keratin 8 and 18 mRNA, HFH8, and T1 alpha mRNA and low levels of surfactant protein A mRNA. At 33 degrees C 20-3 grows with a doubling time of 21 h. At 40 degrees C the majority of cells cease to proliferate. Growth arrest is accompanied by significant morphological changes including an increase in cell size, transition to a squamous phenotype that resembles type 1 cells, and an increase in the number of multinucleated cells within the population. Greater than 95% of the cells incorporate [3H]thymidine into DNA at 33 degrees C whereas at 40 degrees C label incorporation drops to less than 20%. When shifted down to 33 degrees C 40% of the cells remain terminally growth arrested. In addition, cells plated at 40 degrees C have a reduced ability to form colonies when replated at 33 degrees C. Treatment with TGF-beta increases the percentage of cells that terminally growth arrest to greater than 80%. Growth arrest is accompanied by an increase in the levels of c-jun, jun D, cyclin D1, C/EBP-beta, transglutaminase type II, and retinoblastoma (Rb) mRNA and an induction of p105, the hypophosphorylated, growth regulatory form of Rb. Evaluation of Rb mRNA in fetal lung indicates that it is induced 2.5-fold between 17 and 21 days of gestation. These studies indicate that 20-3 terminally growth arrests in culture at the nonpermissive temperature and that it may be useful in studying changes in gene expression that accompany terminal growth arrest during lung development.

Animals↗

PubMed2006

Induction of mesenchymal cell phenotypes in lung epithelial cells by adenovirus E1A.

Epithelial-mesenchymal transformation is now recognised as an important feature of tissue remodelling. The present report concerns the role of adenovirus infection in inducing this transformation in an animal model of chronic obstructive pulmonary disease. Guinea pig primary peripheral lung epithelial cells (PLECs) transfected with adenovirus E1A (E1A-PLECs) were compared to guinea pig normal lung fibroblasts (NLFs) transfected with E1A (E1A-NLFs). These cells were characterised by PCR, immunocytochemistry, electron microscopy, and Western and Northern blot analyses. Electrophoretic mobility shift assays were performed in order to examine nuclear factor (NF)-kappaB and activator protein (AP)-1 binding activities. E1A-PLECs and E1A-NLFs positive for E1A DNA, mRNA and protein expressed cytokeratin and vimentin but not smooth muscle alpha-actin. Both exhibited cuboidal morphology and junctional complexes, but did not contain lamellar bodies or express surfactant protein A, B or C mRNAs. These two cell types differed, however, in their NF-kappaB and AP-1 binding after lipopolysaccharide stimulation, possibly due to differences in the expression of the subunits that comprise these transcriptional complexes. E1A transfection results in the transformation of peripheral lung epithelial cells and normal lung fibroblasts to a phenotype intermediate between that of the two primary cells. It is postulated that this intermediate phenotype may play a major role in the remodelling of the airways in chronic obstructive pulmonary disease associated with persistence of adenovirus E1A DNA.

Actins↗

PubMed2004

Activated T killer cells induce apoptosis in lung epithelial cells and the release of pro-inflammatory cytokine TNF-alpha.

Apoptosis is thought to be involved in lung epithelial cell damage in acute respiratory distress syndrome and interstitial pneumonia. Both the role of apoptosis and its underlying molecular mechanisms in human lung tissue remain unclear. To address these issues, we developed an in vitro assay in which a human lung epithelial cell line and a staphylococcal enterotoxin B (SEB)-reactive human CD8(+) CTL line were co-cultured in the presence of SEB. SEB-stimulated CD8(+) CTL induced apoptosis in the lung epithelial cell line primarily through the perforin/granzyme-mediated pathway. In these cells, apoptosis was initially independent of death receptor pathways. We also tested the effect of IFN-gamma on modulation of apoptosis in lung epithelial cells. In IFN-gamma-pretreated lung epithelial cells, CD95 (APO-1/Fas) activation as well as TNF-related apoptosis-inducing ligand (TRAIL) receptor and TNFR activation led to apoptosis. Furthermore, we found that the interaction of SEB-stimulated CD8(+) CTL with lung epithelial cells induced an increase in TNF-alpha secretion. These results suggest an important role for bacterial superantigen-reactive CD8(+) CTL in induction of lung epithelial cell apoptosis and in modulation of inflammatory processes in lung tissue.

Antigens, Bacterial↗