SCHWANN-CELL EXTRACELLULAR-MATRIX PROTEIN-PRODUCTION IS MODULATED BY MYCOBACTERIUM-LEPRAE AND MACROPHAGE SECRETORY PRODUCTS

Extracellular matrix (ECM) protein deposition is an important feature of leprous nerves, where Schwann cells (SCs) and macrophages are the m ain hosts for Mycobacterium leprae. Since, SCs are involved in the syn thesis of ECM proteins and its production is regulated by macrophage s ecretory factors, the present study aimed to determine in vitro, the e ffect of M. leprae infection and macrophage secretory products on secr etion of ECM proteins by SCs in two strains of mice, Swiss White (SW) and C57BL/6, that are known to differ in their nerve pathology and mac rophage functions in response to infection. Following six days of M. l eprae infection, SCs from SW mice responded with increased secretion o f C-14-leucine radiolabelled proteins and a concomitant increase in la minin and collagens type I, III and IV, as determined by enzyme-linked immunosorbent assay. In contrast infected C57BL/6 SCs responded with decreased secretion of total proteins and fibronectin. Exposure of SCs to macrophage conditioned medium resulted in decreased ECM protein se cretion in both strains of mice. This decrease was a function of prote in breakdown by macrophage derived proteases and also active regulatio n by macrophage secreted cytokines. A similar effect of M. leprae and macrophage secretory products on SC metabolism in leprous nerves would have major ramifications on damage and repair activities. In addition ECM proteins would also influence the composition of the infiltrating cell population in lepromatous and tuberculoid nerves. (C) 1997 Elsev ier Science B.V.