Activated macrophages decrease rat cardiac myocyte contractility: importance of ICAM-1-dependent adhesion.
Macrophages are found in the heart as part of the inflammatory response. To determine whether macrophages could contribute to myocardial dysfunction, rat ventricular myocytes were isolated and cocultured with elicited peritoneal macrophages in media containing tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, or endotoxin for 4 h. Cardiac myocytes were electrically stimulated, and fractional shortening was determined using videomicroscopy. When myocytes alone or myocytes in coculture with macrophages separated by a membrane were challenged with TNF-alpha, lipopolysaccharide, or IL-1, fractional shortening did not decrease. When macrophages were allowed to contact myocytes, fractional shortening decreased from 20. 1 +/- 0.9% in unchallenged macrophage-myocyte cocultures to 15.5 +/- 0.9, 16.3 +/- 0.8, and 15.8 +/- 0.6% when challenged for 4 h with TNF-alpha, endotoxin, or IL-1beta, respectively (P < 0.05). Myocytes had a mean adherence of 4.2 +/- 0.2 macrophages after TNF-alpha challenge compared with 2.6 +/- 0.3 for controls (P < 0.05). The number of adherent macrophages was associated with the decrease in fractional shortening. Anti-intercellular adhesion molecule-1 (ICAM-1) reduced macrophage adherence and prevented the decrease in fractional shortening. This decrease was also prevented by desferoxamine, superoxide dismutase, and nitro-L-arginine methyl ester. This suggests that activated macrophages adhere to myocytes via ICAM-1, and adherent macrophages decrease their contractile function via TNF-alpha, oxygen free radicals, and nitric oxide.
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6.
M G
MG
Simms
K R
KR
Walley
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester