INTRATRACHEAL INJECTION OF ENDOTOXIN AND CYTOKINES .9. CONTRIBUTION OF CD11A ICAM-1 TO NEUTROPHIL EMIGRATION/

Intratracheal injection of endotoxin [lipopolysaccha- ride (LPS)] in r ats causes acute inflammation characterized by the emigration of neutr ophils (PMNs) into the bronchoalveolar airspace. Antibody to PMN adhes ion molecule CD11a inhibited LPS-initiated PMN accumulation in broncho alveolar lavage (BAL) fluid by 32% (P < 0.001). Antibody to the endoth elial CD11a counterreceptor intercellular adhesion molecule-1 (ICAM-1) inhibited LPS-initiated PMN accumulation in BAL fluid by 66% (P < 0.0 001). Combined antibody blockade of ICAM-1 and the C-X-C chemokine cyt okine-induced neutrophil chemoattractant (CINC) inhibited LPS-initiate d PMN emigration by 80%, significantly more than antibody against eith er ICAM-1 or CINC alone. To study the relative contribution of alveola r macrophages and PMNs to intra-alveolar tumor necrosis factor (TNF), the LPS-induced TNF in BAL fluid was measured after depletion of circu lating PMNs with a cytolytic antibody to CD18. Although the anti-CD18 antibody completely abrogated LPS-initiated PMN emigration into BAL fl uid, TNF levels in BAL fluid were unaffected, suggesting that alveolar macrophages are the predominant cellular source of LPS-induced TNF pr oduction. In conclusion, 1) CD11a, ICAM-1, and CINC play major roles i n the LPS-initiated emigration of PMNs into the bronchoalveolar space, and 2) the TNF that drives ICAM-1 and CINC expression is derived larg ely from alveolar macrophages rather than PMNs.