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Cardiovascular Research 2005 68(2):278-288; doi:10.1016/j.cardiores.2005.06.006
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Copyright © 2005, European Society of Cardiology

Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis

Tsuyoshi Yoshida, Haruo Hanawa*, Ken Toba, Hiroshi Watanabe, Ritsuo Watanabe, Kaori Yoshida, Satoru Abe, Kiminori Kato, Makoto Kodama and Yoshifusa Aizawa

Division of Cardiology, Niigata University Graduate School of Medical and Dental Science, 1-754 Asahimachi, Niigata City, 951-8510, Japan

* Corresponding author. Tel.: +81 25 227 2185; fax: +81 25 227 0774. Email address: hanawa{at}med.niigata-u.ac.jp

Background: In a heart with myocarditis, there are cardiomyocytes, inflammatory cells, and non-inflammatory interstitial cells. Immunological molecules are thought to influence not only inflammatory cells but also cardiac function and remodeling. Whatever their origin, the cells they target and the intercellular crosstalk they mediate remain unclear. Here, we examined native gene expression of immunological molecules in normal and rat experimental autoimmune myocarditis (EAM) 18 and 90 days after immunization, using real time RT-PCR in cardiomyocytes, CD11b+ cells, {alpha}βT cells and non-cardiomyocytic non-inflammatory (NCNI) cells.

Methods and results: Cells were isolated by collagenase perfusion on a Langendorff apparatus and purified by passing through a stainless-steel sieve followed by magnetic bead column separation using appropriate monoclonal antibodies. Most immunological molecules were expressed in inflammatory cells. However, some were expressed in NCNI cells or cardiomyocytes. Interestingly, most of interleukin (IL)-10, monocyte chemoattractant protein (MCP)-1, or tumor necrosis factor (TNF)-{alpha} receptor were found in NCNI cells and most of fractalkine were found in NCNI cells and cardiomyocytes. Moreover, TNF-{alpha} significantly upregulated fractalkine and MCP-1 mRNA in cultivated cells from EAM hearts.

Conclusion: In the rat experimental myocarditis heart, inflammatory cells express many immunological molecules. Some of them are thought to influence NCNI cells or cardiomyocytes directly via receptors on these cell types. It is further suggested that fractalkine, IL-10, and MCP-1 expressed in NCNI cells or cardiomyocytes regulate inflammatory cells.

KEYWORDS Myocarditis; Dilated cardiomyopathy; Autoimmunity; Chemokines; Cytokines; Quantitative RT-PCR

Time for primary review 36 days


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