Role of macrophage colony-stimulating factor in polymicrobial sepsis according to studies using osteopetrotic (op/op) mice. 2011

Masahito Ogiku, and Hiroshi Kono, and Kenichi Ishii, and Naohiro Hosomura, and Hideki Fujii
First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.

BACKGROUND The specific purpose of this study was to investigate the role of macrophage colony-stimulating factor (M-CSF)-induced macrophages in mouse polymicrobial sepsis model. METHODS M-CSF deficient (op/op) mice and their littermate mice w ere subjected the cecal ligation and puncture (CLP). Survival was assessed for the following 7 d after the CLP operation, and histopathologic findings were evaluated 12h after CLP. After CLP, expression of inflammatory mediators in serum was assessed by enzyme immunosorbent assay (ELISA). Furthermore, isolated peritoneal macrophages were stimulated with lipopolysaccharide (LPS) (10μg/mL) for 4h, and cytokine concentration in the supernatant was then measured by ELISA. Moreover, phagocytosis of isolated macrophages was assessed using fluorescent rates beads. In another set of experiments, effects of neutralization antibodies against high mobility group box 1 (HMGB1) were investigated in CLP model. RESULTS Mortality was increased in op/op mice compared with op/? mice after CLP. Furthermore, serum HMGB1 levels were also significantly greater in op/op mice than op/? mice. Production of HMGB1 by isolated peritoneal macrophages was significantly greater in op/op mice than op/? mice. Furthermore, the phagocytosis index was significantly blunted in op/op mice compared with op/? mice. Importantly, treatment with neutralization antibodies against HMGB1 markedly prevented acute lung injury and mortality in op/op mice. CONCLUSIONS Matured macrophages by M-CSF play pivotal role by scavenging endotoxin in inflammation. Furthermore, HMGB1 is involved in pathophysiology in polymicrobial sepsis, consistent with previous reports.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008817 Mice, Mutant Strains Mice bearing mutant genes which are phenotypically expressed in the animals. Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D010022 Osteopetrosis Excessive formation of dense trabecular bone leading to pathological fractures; OSTEITIS; SPLENOMEGALY with infarct; ANEMIA; and extramedullary hemopoiesis (HEMATOPOIESIS, EXTRAMEDULLARY). Albers-Schoenberg Disease,Marble Bone Disease,Osteosclerosis Fragilis,Albers-Schonberg Disease,Albers-Schonberg Disease, Autosomal Dominant,Albers-Schönberg Disease,Autosomal Dominant Osteopetrosis Type 2,Congenital Osteopetrosis,Marble Bones, Autosomal Dominant,Osteopetrosis Autosomal Dominant Type 2,Osteopetrosis, Autosomal Dominant 2,Osteopetrosis, Autosomal Dominant, Type II,Osteosclerosis Fragilis Generalisata,Albers Schoenberg Disease,Albers Schonberg Disease,Albers Schonberg Disease, Autosomal Dominant,Albers Schönberg Disease,Disease, Albers-Schoenberg,Disease, Albers-Schonberg,Disease, Albers-Schönberg,Disease, Marble Bone,Osteopetroses,Osteosclerosis Fragilis Generalisatas
D010587 Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES). Phagocytoses
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin
D005260 Female Females

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