title: Mechanisms of enhanced lung injury during sepsis.
abstract: A major complication in sepsis is progressively impaired lung function and susceptibility to intrapulmonary infection. Why sepsis predisposes the lung to injury is not clear. In the current studies, rats were rendered septic by cecal ligation/puncture and evaluated for increased susceptibility to injury after a direct pulmonary insult (deposition of IgG immune complexes or airway instillation of lipopolysaccharide). By itself, cecal ligation/puncture did not produce evidence of lung injury. However, after a direct pulmonary insult, lung injury in septic animals was significantly enhanced. Enhanced lung injury was associated with increased accumulation of neutrophils in lung, enhanced production of CXC chemokines (but not tumor necrosis factor-alpha) in bronchoalveolar lavage fluids, and increased expression of lung vascular intercellular adhesion molecule-1 (ICAM-1). Complement depletion or treatment with anti-C5a abolished all evidence of enhanced lung injury in septic animals. When stimulated in vitro, bronchoalveolar lavage macrophages from septic animals had greatly enhanced CXC chemokine responses as compared with macrophages from sham-operated animals or from septic animals that had been complement depleted. These data indicate that the septic state causes priming of lung macrophages and suggest that enhanced lung injury in the septic state is complement dependent and related to increased production of CXC chemokines.
authors.affiliation: Department of Trauma Surgery, University of Freiburg Medical School, Freiburg/Breisgau, Germany.
authors.forename: B J
authors.initials: BJ
authors.lastname: Czermak
authors.forename: M
authors.initials: M
authors.lastname: Breckwoldt
authors.forename: Z B
authors.initials: ZB
authors.lastname: Ravage
authors.forename: M
authors.initials: M
authors.lastname: Huber-Lang
authors.forename: H
authors.initials: H
authors.lastname: Schmal
authors.forename: N M
authors.initials: NM
authors.lastname: Bless
authors.forename: H P
authors.initials: HP
authors.lastname: Friedl
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D019743:Chemokines, CXC / Q000096:biosynthesis; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D020318:Rats, Long-Evans; D018805:Sepsis / Q000150:complications* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D019138:Antibodies, Blocking; D000936:Antigen-Antibody Complex; D019743:Chemokines, CXC; D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C016310:cobra venom factor; D018799:Intercellular Adhesion Molecule-1; D015936:Complement C5a