PMID- 11021822 OWN - NLM STAT- MEDLINE DCOM- 20001025 LR - 20240413 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 157 IP - 4 DP - 2000 Oct TI - Novel protective effects of stem cell factor in a murine model of acute septic peritonitis. Dependence on MCP-1. PG - 1177-86 AB - Mast cells participate in the host response during sepsis and have been shown to have a protective effect in a murine model of acute septic peritonitis and multi-organ failure initiated by cecal ligation and puncture (CLP). Stem cell factor (SCF) is a hematopoietic cytokine important in mast cell proliferation and activation. In the present study, we examined the protective effects of a single intraperitoneal injection of SCF given 2 hours before CLP surgery in mice. Four days after the CLP surgery, SCF pretreatment significantly improved mouse survival from 29 to 56% and mast cells were absolutely required for this effect. Immunoneutralization studies revealed that the SCF-stimulated release of monocyte chemoattractant protein-1 (MCP-1) into the septic peritoneal cavity contributed to the protective effect of SCF in this model. One potential cellular source of MCP-1 was the SCF-activated mast cell. In addition, SCF pretreatment significantly augmented circulating levels of SCF and the immunomodulatory cytokine interleukin-10 in septic mice, in part because the SCF pretreatment seemed to promote the release of both mediators from the liver. Additional hepatic effects of SCF treatment included an accelerated expression of hepatic levels of signal transducer and activator of transcription-3 (STAT-3) in CLP mice pretreated with SCF. Taken together, the findings from the present study demonstrate that the intraperitoneal delivery of SCF has a major protective effect in a murine model of CLP. FAU - Bone-Larson, C L AU - Bone-Larson CL AD - Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan. University of California, Los Angeles, California, USA. FAU - Hogaboam, C M AU - Hogaboam CM FAU - Steinhauser, M L AU - Steinhauser ML FAU - Oliveira, S H AU - Oliveira SH FAU - Lukacs, N W AU - Lukacs NW FAU - Strieter, R M AU - Strieter RM FAU - Kunkel, S L AU - Kunkel SL LA - eng GR - R01 HL031237/HL/NHLBI NIH HHS/United States GR - HL31237/HL/NHLBI NIH HHS/United States GR - HL60289/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Chemokine CCL2) RN - 0 (DNA-Binding Proteins) RN - 0 (STAT3 Transcription Factor) RN - 0 (Stat3 protein, mouse) RN - 0 (Stem Cell Factor) RN - 0 (Trans-Activators) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Acute Disease MH - Animals MH - Cecum MH - Cell Nucleus/metabolism MH - Chemokine CCL2/metabolism MH - DNA-Binding Proteins/metabolism MH - Female MH - Interleukin-10/metabolism MH - Ligation MH - Liver/drug effects/metabolism MH - Mast Cells/drug effects/pathology/physiology MH - Mice MH - Mice, Inbred Strains MH - Peritonitis/*metabolism/mortality/*pathology MH - Punctures MH - STAT3 Transcription Factor MH - Stem Cell Factor/blood/metabolism/*pharmacology MH - Therapeutic Irrigation MH - Trans-Activators/metabolism MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC1850153 EDAT- 2000/10/06 11:00 MHDA- 2001/02/28 10:01 PMCR- 2001/04/01 CRDT- 2000/10/06 11:00 PHST- 2000/10/06 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/06 11:00 [entrez] PHST- 2001/04/01 00:00 [pmc-release] AID - S0002-9440(10)64633-0 [pii] AID - 2372 [pii] AID - 10.1016/S0002-9440(10)64633-0 [doi] PST - ppublish SO - Am J Pathol. 2000 Oct;157(4):1177-86. doi: 10.1016/S0002-9440(10)64633-0.