Protective effects of anti-neutrophil antibody against myocardial ischemia/reperfusion injury in rats.
Neutrophil activation initiates myocardial ischemia/reperfusion (I/R) injuries. The aim of this study is to evaluate the in vitro functions of an anti-neutrophil monoclonal antibody, Urge-8, and its therapeutic efficacy against myocardial ischemia (MI) in rats. We measured in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. MI was induced in Wistar rats by clamping the left coronary artery for 1 h. Rats received either isotype-negative control IgG(1) (control group, n = 20), 250 microg/kg of Urge-8 before (pre-treatment group, n = 20) or after (post-treatment group, n = 20) MI. The three groups were compared during the first 24 h after reperfusion with respect to changes in mean arterial pressure, heart rate, body temperature, biochemistry, serum cytokines, myocardial neutrophil infiltration, survival rate, and size of MI. Urge-8 effectively suppressed in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. The Urge-8 treated groups showed higher levels of arterial pressure and survival rate, lower values of interleukin-6 and interleukin-8, lower grade of myocardial neutrophil infiltration, and smaller MI size as compared to the control group. In conclusion, Urge-8 is effective against myocardial I/R injury by suppressing certain functions and myocardial infiltration of neutrophils in rats.
Kohtani
T
T
Department of Surgery II, Ehime University School of Medicine, Shitsukawa, Shigenobu, Onsen-gun, Ehime, Japan. kohtani@m.ehime-u.ac.jp
Abe
Y
Y
Sato
M
M
Miyauchi
K
K
Kawachi
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000918:Antibody Specificity; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure; D015153:Blotting, Western; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D007167:Immunotherapy; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007527:Isoenzymes / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000276:immunology / Q000401:mortality / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D009206:Myocardium / Q000166:cytology / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D051381:Rats; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D016209:Interleukin-8; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form