Intratracheal injection of endotoxin and cytokines. IX. Contribution of CD11a/ICAM-1 to neutrophil emigration.
Intratracheal injection of endotoxin [lipopolysaccharide (LPS)] in rats causes acute inflammation characterized by the emigration of neutrophils (PMNs) into the bronchoalveolar airspace. Antibody to PMN adhesion molecule CD11a inhibited LPS-initiated PMN accumulation in bronchoalveolar lavage (BAL) fluid by 32% (P < 0.001). Antibody to the endothelial CD11a counterreceptor intercellular adhesion molecule-1 (ICAM-1) inhibited LPS-initiated PMN accumulation in BAL fluid by 66% (P < 0.0001). Combined antibody blockade of ICAM-1 and the C-X-C chemokine cytokine-induced neutrophil chemoattractant (CINC) inhibited LPS-initiated PMN emigration by 80%, significantly more than antibody against either ICAM-1 or CINC alone. To study the relative contribution of alveolar macrophages and PMNs to intra-alveolar tumor necrosis factor (TNF), the LPS-induced TNF in BAL fluid was measured after depletion of circulating PMNs with a cytolytic antibody to CD18. Although the anti-CD18 antibody completely abrogated LPS-initiated PMN emigration into BAL fluid, TNF levels in BAL fluid were unaffected, suggesting that alveolar macrophages are the predominant cellular source of LPS-induced TNF production. In conclusion, 1) CD11a, ICAM-1, and CINC play major roles in the LPS-initiated emigration of PMNs into the bronchoalveolar space, and 2) the TNF that drives ICAM-1 and CINC expression is derived largely from alveolar macrophages rather than PMNs.
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D002465:Cell Movement; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D006133:Growth Substances / Q000378:metabolism; D007267:Injections; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D014132:Trachea / Q000187:drug effects*
D019743:Chemokines, CXC; D002630:Chemotactic Factors; D016207:Cytokines; D004731:Endotoxins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1