title: Elucidation of the early events contributing to zymosan-induced multiple organ dysfunction syndrome using MIP-1alpha, C3 knockout, and C5-deficient mice.
abstract: Using a zymosan-induced mouse model of multiple organ dysfunction syndrome (MODS), it has been shown that the absence of MIP-1alpha increased mortality fourfold, whereas the absence of C5 decreased mortality fourfold. The purpose of the present study was to determine the early events following zymosan injection in MIP-1alpha knockout and C5-deficient mice. B10.D2/nSnJ (C5-sufficient) and B10.D2/0SnJ (C5-deficient) and genetically matched MIP-1alpha +/+ and MIP-1alpha -/- mice were divided into 3 groups: Group1 received no injection, Group 2 received intraperitoneal saline injection (1.0 mL), and Group 3 were given intraperitoneal zymosan (1 mg/gm, 1.0 mL). Two hours, 24 h, and 48 h after injection, peritoneal exudate leukocyte counts, total WBC count, lung MPO levels, and organ histology were examined for signs of changes in cellular infiltration. An acute local and systemic inflammatory response characterized by an increase in the peritoneal leukocyte count, total WBC counts, and circulating neutrophil levels was observed within 2-48 h of zymosan injection. Lack of MIP-1alpha attenuated local recruitment of phagocytes into the peritoneal cavity, and absence of MIP-1alpha or C5 caused a decrease in circulating neutrophil levels. The presence or absence of either C5 or MIP-1alpha did not affect early pulmonary neutrophil sequestration. Organ histopathology suggested early neutrophil infiltration in the lung and spleen within 48 h. These studies indicate that MIP-1alpha and C5 play a critical role in modulating cellular changes associated with lethality in a zymosan model of MODS.
authors.affiliation: Department of Microbiology and Immunology, University of Louisville School of Medicine, Kentucky 40292, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mahesh
authors.forename: J
authors.initials: J
authors.lastname: Daly
authors.forename: W G
authors.initials: WG
authors.lastname: Cheadle
authors.forename: G J
authors.initials: GJ
authors.lastname: Kotwal
mesh_terms: D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003167:Complement Activation; D003176:Complement C3 / Q000235:genetics* / Q000378:metabolism; D003182:Complement C5 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005122:Exudates and Transudates / Q000166:cytology / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000473:pathology; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D020556:Neutrophil Infiltration; D010538:Peritonitis / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000473:pathology; D000637:Transaminases / Q000378:metabolism; D015054:Zymosan
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003176:Complement C3; D003182:Complement C5; D019402:Macrophage Inflammatory Proteins; D015054:Zymosan; D000637:Transaminases