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], n = 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 IV LPS (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Frevert
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CW
Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115.
Warner
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AE
Kobzik
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L
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002196:Capillaries; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood*; D019041:L-Selectin; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000098:blood supply / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D010537:Peritoneum / Q000166:cytology; D011650:Pulmonary Alveoli / Q000276:immunology; D051381:Rats; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D014115:Toxemia / Q000139:chemically induced / Q000276:immunology*
D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D004731:Endotoxins; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin