title: Antibody to granulocyte macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function after myocardial infarction in a rat coronary artery ligation model.
abstract: Granulocyte macrophage colony-stimulating factor (GM-CSF) promotes infarct expansion and inappropriate collagen synthesis in a myocardial infarction (MI). This study was designed to determine if treatment with anti-GM-CSF will inhibit macrophage migration, preserve function, and limit left ventricular (LV) remodeling in the rat coronary artery ligation model. Treatment with a monoclonal antibody to GM-CSF (5 mg/kg) was initiated 24 hours before coronary artery ligation and continued every 3 days for 3 weeks. Left coronary arteries of rats were ligated, animals were recovered, and cardiac function was evaluated 3 weeks postligation. Tissue samples were processed for histochemistry. Anti-GM-CSF treatment increased LV ejection fraction (37 ± 3% vs 47 ± 5%) and decreased LV end systolic diameter (0.75 ± 0.12 vs 0.59 ± 0.05 cm) with no changes in LV systolic pressure (109 ± 4 vs 104 ± 5 mm Hg), LV end diastolic pressure (22 ± 4 vs 21 ± 2 mm Hg), LV end diastolic diameter (0.96 ± 0.04 vs 0.92 ± 0.05 cm), or the time constant of LV relaxation tau (25.4 ± +2.4 vs 22.7 ± 1.4 milliseconds) (P < 0.05). Significantly lower numbers of tissue macrophages and significant reductions in infarct size were found in the myocardium of antibody-treated animals (81 ± 21.24 vs 195 ± 31.7 positive cells per 0.105 mm, compared with controls. These findings suggest that inhibition of macrophage migration may be beneficial in the treatment of heart failure after MI.
authors.affiliation: Development Engineering Sciences, LLC, Flagstaff, AZ, USA. rskellar@des-company.com
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kellar
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Lancaster
authors.forename: Hoang M
authors.initials: HM
authors.lastname: Thai
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Juneman
authors.forename: Nicholle M
authors.initials: NM
authors.lastname: Johnson
authors.forename: Howard G
authors.initials: HG
authors.lastname: Byrne
authors.forename: Maribeth
authors.initials: M
authors.lastname: Stansifer
authors.forename: Reza
authors.initials: R
authors.lastname: Arsanjani
authors.forename: Mark
authors.initials: M
authors.lastname: Baer
authors.forename: Christopher
authors.initials: C
authors.lastname: Bebbington
authors.forename: Michael
authors.initials: M
authors.lastname: Flashner
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Yarranton
authors.forename: Steven
authors.initials: S
authors.lastname: Goldman
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D006439:Hemodynamics / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D016178:Granulocyte-Macrophage Colony-Stimulating Factor