PMID- 10068207 OWN - NLM STAT- MEDLINE DCOM- 19990401 LR - 20220227 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 79 IP - 2 DP - 1999 Feb TI - Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1. PG - 195-203 AB - MCAF (monocyte chemotactic and activating factor)/MCP-1 (monocyte chemoattractant protein-1) is an important mediator of monocyte recruitment to inflammatory sites. However, its pathophysiologic role in myocardial reperfusion injury remains unknown. Male Wistar rats were anesthetized, and the left anterior descending coronary artery was ligated for an hour, after which the ligature was released. Northern blotting analysis revealed that MCAF/MCP-1 mRNA expression increased 16-fold in the reperfused region at 12 hours after reperfusion. MCAF/MCP-1 concentration in plasma and the heart was already elevated after hour of ischemia in this model. Goat polyclonal antibodies were prepared by repeated immunization of animals with purified, recombinant rat MCAF/MCP-1, and the neutralizing activities of this antibody were confirmed by monocyte chemotaxis assay and administration to rats with crescentic glomerulonephritis. Intravenous injection of anti-MCAF/MCP-1 antibody significantly reduced the infarct size at 24 hours after reperfusion compared with the injection of control IgG (33.9 +/- 5.1% vs 49.4 +/- 2.7% of ischemic area, mean +/- SEM). Administration of this antibody markedly decreased the intercellular adhesion molecule-1 mRNA expression and infiltration of macrophages, which suggested the pathophysiologic role of MCAF/MCP-1. Neutralization of MCAF/MCP-1 is beneficial by preventing reperfusion injury in a rat model of myocardial ischemia and reperfusion. FAU - Ono, K AU - Ono K AD - Department of Cardiovascular Medicine, Kyoto University, Japan. FAU - Matsumori, A AU - Matsumori A FAU - Furukawa, Y AU - Furukawa Y FAU - Igata, H AU - Igata H FAU - Shioi, T AU - Shioi T FAU - Matsushima, K AU - Matsushima K FAU - Sasayama, S AU - Sasayama S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Antibodies) RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Animals MH - Antibodies/*therapeutic use MH - Cell Movement/drug effects/physiology MH - Chemokine CCL2/blood/genetics/*immunology MH - Intercellular Adhesion Molecule-1/genetics MH - Macrophages/drug effects/physiology MH - Male MH - Myocardial Infarction/pathology MH - Myocardial Reperfusion Injury/*prevention & control MH - Osmolar Concentration MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar EDAT- 1999/03/06 00:00 MHDA- 1999/03/06 00:01 CRDT- 1999/03/06 00:00 PHST- 1999/03/06 00:00 [pubmed] PHST- 1999/03/06 00:01 [medline] PHST- 1999/03/06 00:00 [entrez] PST - ppublish SO - Lab Invest. 1999 Feb;79(2):195-203.