FUNCTIONAL-CHARACTERIZATION OF THE RAT CHEMOKINE KC AND ITS IMPORTANCE IN NEUTROPHIL RECRUITMENT IN A RAT MODEL OF PULMONARY INFLAMMATION

Expression of mRNA for the neutrophil (PMN) chemokine, KC, in rat mode ls of lung injury suggests a role for this chemokine in pulmonary infl ammation. We addressed this hypothesis at the protein level by functio nally characterizing recombinant rat KC (rKC) in vitro and in vivo. in vitro, rKC induced PMN chemotaxis and increased the expression of CD11 b/CD18 on PMNs. Recombinant KC also induced a respiratory burst (quant itated by flow cytometry) in rat PMNs, similar to that caused by its h uman structural homologue, gro/melanoma growth-stimulating activity, o n human PMNs, but less than that caused by IL-8 on human PMNs. Intratr acheal instillation of rKC induced dose-dependent PMN influx into airs paces (average PMNs in bronchoalveolar lavage: vehicle = 1.5%, n = 4; rKC (1 mu g) = 11.5%, n = 2; rKC (10 mu g) = 77.3%, n = 2). A neutrali zing anti-KC Ab reduced the chemotactic activity of rat bronchoalveola r ravage fluid collected after the intratracheal administration of LPS (48.3 +/- 8% of control, n = 4). Anti-KC neutralizing Ab markedly inh ibited PMN accumulation (71 +/- 6%) within the lungs in response to an intratracheal challenge of LPS. We conclude that rat KC is a major bu t not exclusive mediator of PMN activation and recruitment during LPS- induced pulmonary inflammation.