ROLE OF NITRIC-OXIDE IN HOST-DEFENSE AGAINST AN EXTRACELLULAR, METAZOAN PARASITE, BRUGIA-MALAYI

The mechanisms by which mammalian hosts eliminate microparasites such as bacteria and viruses are well established, In viral infections, the se mechanisms include the interferons, neutralizing and opsonizing ant ibodies, and cytotoxic T lymphocytes. In bacterial infections, polymor phonuclear leukocytes and macrophages, often facilitated by opsonizing antibodies, ingest the infectious agent and mediate host defense, In addition, complement, in the presence of specific antibodies directed against surface antigens, can lyse certain bacterial pathogens, In con trast, our understanding of the host defenses against metazoan, extrac ellular parasites is less well grounded, We obtained data by two diffe rent approaches to document the role of nitric oxide (NO) as a mediato r of host defense against a human nematode parasite, First, treatment of immunocompetent, nonpermissive mice with an inhibitor of NO synthas e abrogated resistance to Brugia malayi, one of the causative agents o f human lymphatic filariasis, Second, treatment of permissive, immunod eficient mice with a compound that releases NO conferred resistance to infection, These data reinforce studies by James and her coworkers (I . P. Oswald, T. A. Wynn, A. Sher, and S. L. James, Comp. Biochem. Phys iol. Pharmacol. Toxicol. Endocrinol. 108:11-18, 1994) on the role of N O in defense against trematode parasites and of Kanazawa et al. (T, Ka nazawa, H. Asahi, H. Hata; K. Machida, N. Kagei, and M. J. Stadecker, Parasite Immunol. 15:619-623, 1993) on cestode parasites.