Lipopolysaccharide-induced pulmonary vascular sequestration of polymorphonuclear leukocytes is complement independent.
Lipopolysaccharide (LPS) injected intravenously produces leukopenia and sequestration of polymorphonuclear leukocytes (PMN) in the pulmonary vascular bed. To evaluate the role of complement in this process, we used C5-sufficient (B10.D2/nSn) and C5-deficient (B10.D2/oSn) mice and Sprague-Dawley rats depleted of complement with Naja naja cobra venom factor (CVF). We found a comparable increase in the number of PMN in lung tissue of C5-sufficient and C5-deficient mice given Escherichia coli LPS (0127:B8, 3 mg/kg), revealing that LPS acts independently of C5 and its biologically active fragments. Intravenous injection of LPS (3 mg/kg) into rats caused significant intravascular complement activation as assessed by serum CH50 and resulted in an almost 10-fold increase in numbers of PMN in lung tissue. Pretreatment of rats with CVF (50 U) did not reduce LPS-induced PMN sequestration, suggesting that the process is independent of C3. As reported previously, we found large numbers of PMN in bronchoalveolar lavage samples of 24 h after injection of LPS (3 mg/kg). Complement depletion did not prevent LPS-induced migration of PMN. No PMN migration occurred 2, 6, 12, 24, or 48 h after injection of CVF alone, indicating that complement activation is not sufficient to cause PMN migration. In contrast to our findings in rats, no PMN migrated into airspaces of C5-sufficient and C5-deficient mice 24 or 48 h after injection of LPS (3 to 20 mg/kg).
Cardozo
C
C
Department of Medicine, Mount Sinai School of Medicine, New York, New York.
Edelman
J
J
Jagirdar
J
J
Lesser
M
M
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002465:Cell Movement / Q000187:drug effects; D003167:Complement Activation; D003182:Complement C5 / Q000172:deficiency / Q000502:physiology*; D015941:Complement Hemolytic Activity Assay; D004546:Elapid Venoms / Q000494:pharmacology; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000473:pathology*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D003182:Complement C5; D004546:Elapid Venoms; D008070:Lipopolysaccharides