title: Role of complement in endotoxin/platelet-activating factor-induced lung injury.
abstract: C receptor-1 is a protein involved in the regulation of C3 and C5-convertases. Recombinant human soluble C receptor-1 has recently been produced and shown to reduce infarct size in a rat model of myocardial ischemia/reperfusion injury. The present study aimed to investigate whether recombinant human soluble C receptor-1 exerts any protective effect on pulmonary injury produced in a rodent model of adult respiratory distress syndrome. In this model, Escherichia coli endotoxin (LPS, 0.1 microgram/kg) combined with platelet-activating factor (1 pmol/kg/min over 60 min, n = 10) caused microvascular lung injury characterized by elevation of myeloperoxidase activity, deposition of C3 and C5b-9 on the endothelium of pulmonary vessels, and pulmonary edema. Furthermore, bronchoalveolar lavage revealed increased neutrophil count and elevated protein concentration. These pulmonary responses were associated with elevated serum TNF-alpha. Pretreatment (10 min, i.v.) with recombinant human soluble C receptor-1 at 10 mg/kg (n = 13), but not at 1 mg/kg, prevented the LPS/platelet-activating factor-induced pulmonary edema (p less than 0.01) and changes in the bronchoalveolar lavage fluid cell count (p less than 0.01) and protein concentration (p less than 0.05), and attenuated the deposition of C3 and C5b-9 to lung vessels. There was no effect on lung myeloperoxidase activity and serum TNF-alpha. Also, C depletion by cobra venom factor (500 U/kg, i.v.) eliminated the pulmonary edema and elevated leukocyte count in bronchoalveolar lavage fluid, but had no effect on lung myeloperoxidase activity and serum TNF-alpha. These data suggest that C factors may play an important role in the pathophysiology of adult respiratory distress syndrome.
authors.affiliation: Department of Surgery, Jefferson Medical College, Philadelphia, PA 19107-5083.
authors.forename: R
authors.initials: R
authors.lastname: Rabinovici
authors.forename: C G
authors.initials: CG
authors.lastname: Yeh
authors.forename: L M
authors.initials: LM
authors.lastname: Hillegass
authors.forename: D E
authors.initials: DE
authors.lastname: Griswold
authors.forename: M J
authors.initials: MJ
authors.lastname: DiMartino
authors.forename: J
authors.initials: J
authors.lastname: Vernick
authors.forename: K L
authors.initials: KL
authors.lastname: Fong
authors.forename: G
authors.initials: G
authors.lastname: Feuerstein
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003165:Complement System Proteins / Q000502:physiology*; D004546:Elapid Venoms / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity*; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects*; D008297:Male; D009195:Peroxidase / Q000032:analysis; D010972:Platelet Activating Factor / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011951:Receptors, Complement / Q000502:physiology; D017463:Receptors, Complement 3b; D012128:Respiratory Distress Syndrome / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D003176:Complement C3; D015938:Complement Membrane Attack Complex; D004546:Elapid Venoms; D004731:Endotoxins; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha; C016310:cobra venom factor; D003165:Complement System Proteins; D009195:Peroxidase