PMID- 11751168 OWN - NLM STAT- MEDLINE DCOM- 20020131 LR - 20141120 IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 282 IP - 1 DP - 2002 Jan TI - MCP-1 causes leukocyte recruitment and subsequently endotoxemic ileus in rat. PG - G145-55 AB - Endotoxemia causes an inflammatory response within the intestinal muscularis and gastrointestinal dysmotility. We hypothesize that the resident macrophage-derived chemokine monocyte chemoattractant protein-1 (MCP-1) plays a significant role in the recruitment of leukocytes into the lipopolysaccharide (LPS)-stimulated rat intestinal muscularis. MCP-1 mRNA expression was investigated by RT-PCR. Leukocyte extravasation and MCP-1 protein localization were determined by immunohistochemistry. Contractile activity was assessed by using a standard organ bath in rats that were treated with saline, recombinant MCP-1, LPS, LPS + nonspecific antibody, or LPS + MCP-1 antibody. Endotoxemia caused a significant 280-fold increase in MCP-1 mRNA expression in the muscularis, peaking at 3 h. MCP-1 protein was immunohistochemically located to muscularis macrophages. LPS application caused significant leukocyte recruitment into the muscularis and a 51% decrease in muscle contractility. MCP-1 antibody treatment significantly averted leukocyte recruitment and significantly prevented muscle dysfunction. These parameters were not significantly altered by the nonspecific antibody. Results show that resident muscularis macrophage-derived MCP-1 plays a major role in the recruitment of monocytes during endotoxemia, which then subsequently secrete kinetically active substances that cause ileus. FAU - Turler, Andreas AU - Turler A AD - Department of Medicine, Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA. FAU - Schwarz, Nicolas T AU - Schwarz NT FAU - Turler, Esther AU - Turler E FAU - Kalff, Jorg C AU - Kalff JC FAU - Bauer, Anthony J AU - Bauer AJ LA - eng GR - P50-GM-53789/GM/NIGMS NIH HHS/United States GR - R01-GM-58241/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (Antibodies) RN - 0 (Chemokine CCL2) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Antibodies/pharmacology MH - Chemokine CCL2/*genetics/immunology/*pharmacology MH - Chemotaxis, Leukocyte/*drug effects MH - Endotoxemia/*immunology/physiopathology MH - Gastrointestinal Motility/immunology MH - Gene Expression/drug effects/immunology MH - Immunohistochemistry MH - In Vitro Techniques MH - Intestinal Obstruction/*immunology/physiopathology MH - Lipopolysaccharides/pharmacology MH - Macrophages/physiology MH - Male MH - Muscle, Smooth/immunology/physiopathology MH - RNA, Messenger/analysis MH - Rats MH - Rats, Inbred ACI EDAT- 2001/12/26 10:00 MHDA- 2002/02/01 10:01 CRDT- 2001/12/26 10:00 PHST- 2001/12/26 10:00 [pubmed] PHST- 2002/02/01 10:01 [medline] PHST- 2001/12/26 10:00 [entrez] AID - 10.1152/ajpgi.00263.2001 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2002 Jan;282(1):G145-55. doi: 10.1152/ajpgi.00263.2001.