title: Lipopolysaccharide-induced pulmonary vascular sequestration of polymorphonuclear leukocytes is complement independent.
abstract: 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).
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York.
authors.forename: C
authors.initials: C
authors.lastname: Cardozo
authors.forename: J
authors.initials: J
authors.lastname: Edelman
authors.forename: J
authors.initials: J
authors.lastname: Jagirdar
authors.forename: M
authors.initials: M
authors.lastname: Lesser
mesh_terms: 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
chemical_list: D003182:Complement C5; D004546:Elapid Venoms; D008070:Lipopolysaccharides