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Activated macrophages decrease rat cardiac myocyte contractility : importance of ICAM-1 dependent adhesion

University of British Columbia

Macrophages are found in the heart as part of the inflammatory response. Our goal was to determine whether macrophages could contribute to myocardial dysfunction. Rat ventricular myocytes were isolated using a collagenase perfusion system and cultured for 24 hours. Then myocytes were co-cultured with elicited peritoneal macrophages in media alone or in media containing TNFα IL-1β or endotoxin for 4 hours. Myocytes were electrically stimulated and fractional shortening was determined using videomicroscopy. When myocytes alone were challenged with TNFα, or LPS, fractional shortening did not decrease. When macrophages were prevented from adhering to myocytes by well inserts, TNFα and LPS did not have an effect. Fractional shortening of myocytes decreased from 20.3 ± 1.1% in unchallenged macrophage-myocyte co-cultures, without inserts, to 15.3 ± 1.1% and 15.1 ±1.8% when challenged for 4 hours with TNFα or endotoxin respectively (p<0.05). After 4 hours, the challenged myocytes had a mean adherence of 4.2 ± 0.2 macrophages compared to 2.6 ± 0.3 for controls (p<0.05). The number of adherent macrophages was associated with the decrease in fractional shortening. ELISA showed dose dependent ICAM-1 expression on myocytes, while VCAM-1 did not induce measurable expression. Antibody to ICAM-1 reduced macrophage adherence and prevented the decrease in fractional shortening. The decrease in fractional shortening was also prevented by anti-TNFα, desferoxamine, SOD, and L-NAME. These results suggest that activated macrophages adhere to cardiac myocytes via ICAM-1 and adherent macrophages decrease cardiac myocyte contractile function via TNFα, oxygen free radicals, and nitric oxide.

Thesis/Dissertation

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2009-05-04

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http://hdl.handle.net/2429/7864

Experimental Medicine

University of British Columbia

UBCV

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