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, these mechanisms include the interferons, neutralizing and opsonizing antibodies, and cytotoxic T lymphocytes. In bacterial infections, polymorphonuclear 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 contrast, our understanding of the host defenses against metazoan, extracellular parasites is less well grounded. We obtained data by two different approaches to document the role of nitric oxide (NO) as a mediator of host defense against a human nematode parasite. First, treatment of immunocompetent, nonpermissive mice with an inhibitor of NO synthase abrogated resistance to Brugia malayi, one of the causative agents of human lymphatic filariasis. Second, treatment of permissive, immunodeficient 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. Physiol. Pharmacol. Toxicol. Endocrinol. 108:11-18, 1994) on the role of NO in defense against trematode parasites and of Kanazawa et al. (T. Kanazawa, H. Asahi, H. Hata; K. Machida, N. Kagei, and M. J. Stadecker, Parasite Immunol. 15: 619-623, 1993) on cestode parasites.
Rajan
T V
TV
Department of Pathology, University of Connecticut Health Center, Farmington, USA.
Porte
P
P
Yates
J A
JA
Keefer
L
L
Shultz
L D
LD
D000330:Aedes; D000818:Animals; D017178:Brugia malayi / Q000276:immunology*; D004048:Diethylamines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005368:Filariasis / Q000276:immunology*; D006146:Guanidines / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009589:Nitrogen Oxides
D004048:Diethylamines; D004791:Enzyme Inhibitors; D006146:Guanidines; D009589:Nitrogen Oxides; D009569:Nitric Oxide; C087229:diethylamine dinitric oxide adduct; D019001:Nitric Oxide Synthase; C004479:pimagedine