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University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6
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-
(TNF-
), interleukin (IL)-1
, 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-
, 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-
, endotoxin, or
IL-1
, respectively (P < 0.05).
Myocytes had a mean adherence of 4.2 ± 0.2 macrophages after
TNF-
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-
, oxygen free radicals,
and nitric oxide.
ischemia-reperfusion; sepsis; tumor necrosis factor-
; intercellular adhesion molecule-1
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