Journal of Neurological Sciences 151 (1997) 13–22 Schwann cell extracellular matrix protein production is modulated by Mycobacterium leprae and macrophage secretory products * Neeta Singh, Tannaz J. Birdi , Sushila Chandrashekar, Noshir H. Antia The Foundation for Medical Research, 84- A, R.G. Thadani Marg, Worli, Bombay 400 018, India Received 23 October 1996; revised 10 March 1997; accepted 25 March 1997 Abstract Extracellular matrix (ECM) protein deposition is an important feature of leprous nerves, where Schwann cells (SCs) and macrophages are the main hosts for Mycobacterium leprae. Since, SCs are involved in the synthesis of ECM proteins and its production is regulated by macrophage secretory factors, the present study aimed to determine in vitro, the effect of M. leprae infection and macrophage secretory products on secretion 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 macrophage functions in response to infection. Following six days of M. leprae infection, SCs from SW mice 14 responded with increased secretion of C-leucine radiolabelled proteins and a concomitant increase in laminin 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 secretion in both strains of mice. This decrease was a function of protein breakdown by macrophage derived proteases and also active regulation 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.  1997 Elsevier Science B.V. Keywords: Schwann cells; Mycobacterium leprae; Macrophages; Laminin; Collagens; Fibronectin 1. Introduction Previous studies have shown that the ability of SCs to ensheath and myelinate axons depends on deposition of the Collagens, laminin and fibronectin form the bulk of the BL and absence of any of the BL components can lead to extracellular matrix (ECM) proteins found in the peripher- aberrant SC–axon associations (Eldridge et al., 1989; al nerve. Collagens type I and type III are localised in the Obremski et al., 1993) resulting in severe neurological interstitial spaces of the epineurium, perineurium and the manifestations (Okada et al., 1980; Cornbrooks et al., endoneurium. Collagen types IV and V, laminin and 1983). Besides this, all the three ECM proteins promote fibronectin are constituents of the basal lamina (BL) that neurite outgrowth and therefore play an important role in surrounds each Schwann cell (SC)–axon unit and the peripheral nerve regeneration (Manthorpe et al., 1983; perineurial layers (Shellswell et al., 1979; Sanes, 1982). Adler et al., 1985). On the other hand excessive deposition Over the last two decades sufficient evidence has emerged of ECM proteins, mainly collagens and fibronectin, leads that show SCs to be one of the major contributors of neural to tissue scarring and fibrosis in chronic progressive ECM proteins (Bunge et al., 1980; Carey et al., 1983). conditions that in time obliterate the tissue structure (Haralson, 1993). * Macrophages, which have been shown to be actively Corresponding author. Tel.: 191 22 4934989 / 191 22 4932876; Fax: 191 22 2662735. involved in assisting SCs in peripheral nerve repair (Perry 0022-510X / 97 / $17.00  1997 Elsevier Science B.V. All rights reserved PII S0022-510X(97)00105-6