MCP-1 causes leukocyte recruitment and subsequently endotoxemic ileus in rat.
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.
Türler
Andreas
A
Department of Medicine, Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.
Schwarz
Nicolas T
NT
Türler
Esther
E
Kalff
Jörg C
JC
Bauer
Anthony J
AJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D019446:Endotoxemia / Q000276:immunology* / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007415:Intestinal Obstruction / Q000276:immunology* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011912:Rats, Inbred ACI
D000906:Antibodies; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D012333:RNA, Messenger