Overexpression of neural cell adhesion molecule in Chagas' myocarditis

The expression of the neural cell adhesion molecule (NCAM) was studied in n ormal human myocardium and in Chagas' disease myocarditis. We found that NC AM is expressed in the conduction system as well as the myocardium in the f etal heart, but its expression is restricted to the conduction system and a bsent in the adult myocardium. Chagas' disease is an American endemic disea se caused by the Trypanosoma cruzi parasite, which produces myocarditis and a blockade of the conduction system, resulting in cardiac dysfunction. We studied the expression of NCAM in paraffin-embedded human heart tissues fro m 34 autopsies of patients with Chagas' myocarditis and from murine and can ine experimental acute Chagas' myocarditis, using a polyclonal anti-NCAM an tibody and immunohistochemistry. Our results show a dramatic upregulation o f NCAM expression in the intercalated discs of cardiomyocytes in acute and chronic Chagas' myocarditis, Surprisingly, the NCAM signal was detected in intracellular nests of amastigote forms of the parasite, within infected ca rdiomyocytes of human and experimental Chagas' myocarditis. In contrast, ca rdiac cell-cell adhesion proteins, N-cadherin and beta -catenin, were found in intercalated discs distorted by the infection but absent from the amast igote nests. Proteins reactive to several antibodies against NCAM were dete cted by Western immunoblotting in cultured T cruzi parasites and in trypoma stigote forms of T cruzi extracted from the blood of infected mice. The upr egulation of NCAM in Chagas' myocarditis and the expression of NCAM or a NC AM-like protein by T cruzi suggest that NCAM may act as a receptor for tiss ue targeting and cellular invasion by T cruzi in Chagas' disease. HUM PATHO L 32:149-155. Copyright (C) 2001 by W.B. Saunders Company.