Multinucleated giant cells (MGC) have been long recognized as a histopathologic feature of tuberculosis, yet little is known about the underlying mechanism of tubercle bacillus-induced formation of these fused macrophages. The main purpose of this study was to characterize cellular mechanisms involved in MGC formation of swine microglia, the resident macrophages of the brain, in cultures containing nonopsonized Mycobacterium bovis. Within 2 h of incubation. MGC were readily detected in these cultures by light and transmission electron microscopy. MGC formation was blocked by anti-CD14 and anti-CD18 antibodies and by thalidomide, a potent inhibitor of tumor necrosis factor-α (TNF-α) production by microglia. Also, TNF-α alone induced MGC formation. These findings suggest that two microglial cell receptors, CD14 and a β2 integrin, and the cytokine TNF-α participate in M. bovis-induced swine microglial MGC formation.
Bibliographical noteFunding Information:
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, and Departments ofMedicine and Pathology, Hennepin County Medical Center, and University of Minnesota Medical School, Minneapolis; College of Veterinary Medicine, University ofMinnesota, St. Paul, Minnesota
Received 12 October 1995; revised 14 December 1995. Neonatal swine brain tissue was obtained under a protocol approved by the institutional animal care, use, and research committee. Grant support: National Institutes of Health (DA-0438l and DA-08496). Reprints or correspondence: Dr. Phillip K. Peterson, Dept. of Medicine, Hennepin County Medical Center, 701 Park Ave., Minneapolis, MN 55415.