Primary human alveolar epithelial cells can elicit the transendothelial migration of CD14+ monocytes and CD3+ lymphocytes.
The ability of freshly isolated primary human alveolar epithelial cells (type II pneumocytes) to induce leucocyte migration across an endothelial monolayer was investigated. Three-way factorial analysis of variance (ANOVA) demonstrated that resting alveolar endothelial cells (AEC) could produce detectable quantities of monocyte chemoattractant protein 1 (MCP-1), which was upregulated in response to tumour necrosis factor-alpha (TNF-alpha) in a dose- and time-dependent fashion. Interferon-gamma (IFN-gamma) had no significant effect on this process. TNF-alpha and IFN-gamma both induced AEC to provoke migration of CD14+ monocytes and CD3+ lymphocytes across endothelium. IFN-gamma and TNF-alpha synergized in their ability to induce production of T lymphocyte, but not monocyte, chemoattractants from AEC. Leucocyte transendothelial migration was inhibited by anti-MCP-1 neutralizing antibody and by heparin, a polyanionic glycosaminoglycan (GAG). These data suggest that human AEC play a role in the multiple mechanisms that facilitate monocyte and T lymphocyte migration into the alveolar compartment of the lung under homeostasis and inflammatory conditions. One of these mechanisms is mediated via constitutive MCP-1 production by alveolar epithelial cells, which is upregulated by TNF-alpha.
School of Sciences, University of Sunderland, Sunderland, UK.
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Eghtesad
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HE
Jackson
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Cunningham
D017252:CD3 Complex / Q000032:analysis; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004727:Endothelium / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D009000:Monocytes / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D017252:CD3 Complex; D018932:Chemokine CCL2; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma