IN-VITRO STUDIES ON EXTRACELLULAR-MATRIX PRODUCTION BY MYCOBACTERIUM-LEPRAE INFECTED MURINE NEUROFIBROBLASTS

Fibroblasts and a host of macrophage secretory products have been impl icated in a number of diseases where excess extracellular matrix (ECM) deposition is the main pathological feature. Fibrosis characterized b y excessive deposition of collagen also contributes to the irreversibl e nerve damage observed in leprosy. Since M. leprae are seen within ne urofibroblasts (Nf) in the advanced stages of the disease and macropha ges form a common infiltrating cellular constituent of leprous nerves at all stages, secretion of ECM proteins by Nf was studied, in vitro f ollowing infection with M. leprae and in the presence of macrophage se cretory products. These studies were compared in cells derived from tw o strains of mice, Swiss White (SW) and C57BL/6, as they differ in the ir response to M. leprae infection and parallel those observed in lepr omatous and tuberculoid patients, respectively. On infection with M. l eprae, Nfs showed a decrease in secretion of collagen type IV in SW an d type I in C57B1/6 strain. Macrophages caused a further decrease in t he secretion of collagen types affected by M. leprae infection per se, while the other collagen types, viz. I and III in SW strain and III a nd IV in C57B1/s strain, were unaffected. This study indicates that ne ural collagenization in nerves in advanced leprosy may be of Nf origin . However, unlike other diseases with excess collagen deposition, ECM proteins produced by Nfs in response to nerve damage may not be of pri me importance in the progression of leprous neuropathy and occur as a general response to loss of cellular content in leprous nerves.