CARDIAC MYOCYTES RELEASE LEUKOCYTE-STIMULATING FACTORS

The production of cytokines directly from cardiac myocytes has not bee n previously demonstrated and could represent an important mechanism a nd site of intervention in ischemia and reperfusion injuries. Macropha ge inflammatory protein-2 (MIP-2) and monocyte chemotactic protein (MC P) are chemotactic cytokines (chemokines) that stimulate polymorphonuc lear leukocytes (PMNs) and monocytes, respectively. Endothelium has be en implicated as being a major cellular source of leukocyte-activating factors. We hypothesized that the myocardial cells may also play an i mportant role in producing chemokines independently of endothelium. Pr imary cultures of adult rat ventricular myocytes were prepared. Cultur ed myocytes were stimulated with either interleukin 1 (IL-1), tumor ne crosis factor (TNF), or lipopolysaccharide (LPS). MIP-2 and MCP mRNA w ere expressed in adult rat myocytes following stimulation. Our studies indicate that ventricular myocytes expressed chemokine mRNA and prote in in both a dose- and time-dependent fashion. MIP-2 and MCP release, determined by enzyme-linked immunosorbent assay, was biologically acti ve, accounting for similar to 40% of the PMN and monocyte chemotactic activity produced by these cells. These results suggest that cardiac m yocytes may directly recruit activated leukocytes into areas of injury . Such a recruiting process could underlie the migration of leukocytes into areas of oxidant stress and play a role in development of reperf usion injury of myocardium.