Effect of nitric oxide synthase inhibition on Schistosoma japonicum egg-induced granuloma formation in the mouse liver.
Nitric oxide (NO) plays diverse roles in a variety of pathological processes. We investigated the role of NO in Schistosoma japonicum egg-induced granuloma formation in a mouse hepatic model. Immunohistological analysis revealed that there is the most intense and extensive inducible nitric oxide (iNOS) expression 2 weeks after egg implantation, and thereafter it decreased considerably with time. Treatment with nitric oxide synthase inhibitors, NIL (L-N6- (iminoethyl)-lysine) or N(omega)-nitro-L-arginine methyl ester (L-NAME), resulted in two different types of unusual granulomas at 2 weeks. One type showed suppressed fibrosis, while another showed foreign body-type multinuclear cell formation which frequently appeared particularly when 50 microg/ml NIL was given. At 3 weeks following treatment, fibrotic granulomas with scanty peripheral cellularity was obvious. However, there were no apparent changes after this period (at 4 weeks). Cytokine analysis in NIL-treated mice showed a significant increase of IL-4 and IL-13 production at 2 weeks. These findings indicated that nitric oxide contributes to granuloma development during the early stages, probably through the regulation of Th2 cytokine production.
Hirata
M
M
Department of Parasitology, Kurume University School of Medicine, Kurume, Japan. hiramizu@med.kurume-u.ac.jp
Hirata
K
K
Kage
M
M
Zhang
M
M
Hara
T
T
Fukuma
T
T
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005355:Fibrosis / Q000276:immunology; D006099:Granuloma / Q000201:enzymology / Q000469:parasitology*; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008107:Liver Diseases / Q000469:parasitology* / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000201:enzymology / Q000276:immunology*
D004791:Enzyme Inhibitors; D018793:Interleukin-13; C090663:N(6)-(1-iminoethyl)lysine; D015847:Interleukin-4; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester