title: Properdin deficiency in murine models of nonseptic shock.
abstract: Hereditary properdin deficiency is linked to susceptibility to meningococcal disease (Neisseria meningitidis serotypes Y and W-135) with high mortality. Its relative contribution toward the outcome of nonseptic shock has not been investigated. Using properdin-deficient C57BL/6 mice and their littermates, this study examines their survival of zymosan-induced and LPS-induced shock. Properdin-deficient mice were more resistant to zymosan shock compared with wild-type mice, which showed greater impairment of end-organ function 24 h after zymosan injection, higher TNF-alpha production by alveolar and peritoneal macrophages, higher TNF-alpha, and, inversely, lower IL-10 levels in peritoneal lavage and circulation and higher plasma C5a levels. Properdin-deficient mice showed significantly higher mortality in LPS shock, elevated TNF-alpha, and, inversely, reduced IL-10 production by peritoneal macrophages as well as lower plasma C5a levels compared with wild-type littermates. NO production by peritoneal macrophages and plasma alpha1-antitrypsin levels at 24 h after the injection of LPS or zymosan were decreased in properdin-deficient mice in both models, and fewer histopathologic changes in liver were observed in properdin-deficient animals. This study provides evidence that properdin deficiency attenuates zymosan-induced shock and exacerbates LPS-induced shock.
authors.affiliation: Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Nina D
authors.initials: ND
authors.lastname: Ivanovska
authors.forename: Petya A
authors.initials: PA
authors.lastname: Dimitrova
authors.forename: Jeni C
authors.initials: JC
authors.lastname: Luckett
authors.forename: Rana
authors.initials: R
authors.lastname: El-Rachkidy Lonnen
authors.forename: Wilhelm J
authors.initials: WJ
authors.lastname: Schwaeble
authors.forename: Cordula M
authors.initials: CM
authors.lastname: Stover
mesh_terms: D000818:Animals; D015936:Complement C5a / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000096:biosynthesis; D011414:Properdin / Q000172:deficiency*; D012769:Shock / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan / Q000633:toxicity*; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin; D011414:Properdin; D016753:Interleukin-10; D009569:Nitric Oxide; D015936:Complement C5a; D015054:Zymosan