DEFECTIVE PULMONARY RECRUITMENT OF NEUTROPHILS IN A RAT MODEL OF ENDOTOXEMIA

We have characterized a defect in the pulmonary recruitment of neutrophils (PMNs) in rats with experimental endotoxemia. Rats pretreated with intravenous (IV) 0.9% saline (NaCl) showed abundant PMNs in bronchoalveolar lavage (BAL) fluid after intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) (54.27 +/- 9.80 x 10(6), n = 7, versus IT saline, 0.73 +/- 0.62 x 10(6), n = 4). In contrast, endotoxemic rats (IV LPS 1.0 mg/kg) failed to show PMN influx after IT LPS (0.40 +/- 0.13 x 10(6) PMNs in BAL fluid, n = 7). Four hours after the IT administration of LPS, the chemotactic activity of BAL fluid from endotoxemic rats (87 +/- 9.92% of maximal chemotaxis toward zymosan-activated serum [ZAS], rt = 4) was not significantly different (P > 0.05) from rats pretreated with IV NaCl (61.09 +/- 6.17% of maximal chemotaxis toward ZAS. n = 4). Endotoxemic and control rats showed similar chemotactic gradients in determinations of the BAL/plasma chemotactic activity ratio (BAL/plasma ratio: 2.16 +/- 0.14, n 4, IV NaCl versus 2.98 +/- 0.14, n = 4, IV LPS, P > 0.05). Serum from untreated rats, rats pretreated with IV NaCl, and endotoxemic rats caused minimal effects on rat PMN chemotaxis in vitro (78.17 +/- 8.16%, 79.29 +/- 7.09%, and 69.28 +/- 9.04% of maximal chemotaxis toward ZAS, respectively, n 4/group, P > 0.05). Quantitation of PMN adhesion molecules revealed a loss of L-selectin (8 +/- 5% of control group, n = 3), an increase in Mac-1 (776 +/- 82.60% of control group, n = 3), and no change in LFA-1 when normal PMNs were incubated with plasma from rats pretreated with TV LPS (P < 0.05). Intratracheal challenge with LPS in endotoxemic rats provides a useful model of defective pulmonary PMN recruitment. Alterations in L-selectin and Mac-1 levels on PMNs suggest that ineffective PMN-endothelial cell interactions could be involved.