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Journal of Histochemistry and Cytochemistry, Vol. 51, 625-631, May 2003, Copyright © 2003, The Histochemical Society, Inc.


ARTICLE

Expression of Macrophage Migration Inhibitory Factor in Acute Ischemic Myocardial Injury

Cheuk-Man Yua, Kevin Wing-Hon Laib, Yong-Xiong Chenb, Xiao-Ru Huangc, and Hui Y. Lanc
a Division of Cardiology, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong
b Division of Cardiology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong
c Division of Nephrology, Baylor College of Medicine, Houston, Texas

Correspondence to: Cheuk-Man Yu, Dept. of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong. E-mail: cmyu@cuhk.edu.hk

Macrophage migration inhibitory factor (MIF) is a key mediator in inflammatory or immune-mediated diseases, although its role in heart diseases is unknown. This study investigated the expression of MIF in the myocardium in the development of acute myocardial infarction (AMI). By use of immunohistochemistry, Western blotting, RT-PCR, and in situ hybridization, the gene and protein expression of MIF in the heart at 6 hr, 1 day, 3 days, 1 week, and 2 weeks after AMI was studied. In both normal and sham-operated rats, MIF mRNA and protein were expressed constitutively at low levels by the myocytes. By contrast, MIF mRNA was rapidly upregulated by the surviving myocytes in the infarcted region and, to a lesser extent, the non-infarcted region, accounting for a sevenfold increase at 6 hr after AMI (p<0.001). This was followed by a fourfold increase in MIF protein expression at day 1 after AMI (p<0.05). Macrophages were found accumulated in the infarcted region, being significant at day 1 (p<0.01) and progressive increased over the 2-week time course (p<0.01) in which MIF was found expressed in these cells. The results indicated that the infiltrating macrophages and myocytes were sources of MIF in the infarcted region. The latter cells became activated and involved in the amplification of inflammatory response in AMI. Therefore, upregulation of myocardial MIF may contribute to macrophage accumulation in the infarcted region and their pro-inflammatory role may participate in the myocyte damage seen in AMI. (J Histochem Cytochem 51:625–631, 2003)

Key Words: macrophage migration, inhibitory factor, macrophages, myocytes, myocardial infarction, gene expression


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