MULTINUCLEATED GIANT-CELL FORMATION OF SWINE MICROGLIA INDUCED BY MYCOBACTERIUM-BOVIS

Multinucleated giant cells (MGC) have been long recognized as a histop athologic feature of tuberculosis, yet little is known about the under lying mechanism of tubercle bacillus-induced formation of these fused macrophages. The main purpose of this study was to characterize cellul ar mechanisms involved in MGC formation of swine microglia, the reside nt macrophages of the brain, in cultures containing nonopsonized Mycob acterium bovis. Within 2 h of incubation, MGC were readily detected in these cultures by light and transmission electron microscopy. MGC for mation was blocked by anti-CD14 and anti-CD18 antibodies and by thalid omide, a potent inhibitor of tumor necrosis factor-alpha (TNF-alpha) p roduction by microglia. Also, TNF-alpha alone induced MGC formation. T hese findings suggest that two microglial cell receptors, CD14 and a b eta(2) integrin, and the cytokine TNF-alpha participate in M. bovis-in duced swine microglial MGC formation.