Expression of arginase I and inducible nitric oxide synthase in the peripheral blood and lymph nodes of HIV-positive patients

ZHANG, NAICHUN; DENG, JIANNING; WU, FENGYAO; LU, XIANGCHAN; HUANG, LEI; ZHAO, MIN

Helicobacter pylori and Toxoplasma gondii, may use arginine to induce inflammation-associated immune suppression, leading to immune evasion (12, 31, 32, 39) . In the NOS pathway, L-arginine is metabolized by iNOS into citrulline and NO, and NO is important in the destruction of cancer cells, viruses, bacteria and parasites and in regulation of a variety of immune cells (40) . NOS has three isoforms, which include two constitutive isoforms, neural NOS and endothelial NOS, and one inducible isoform (iNOS) (41) . Constitutive NOS is predominantly involved in the physiological synthesis of NO and the regulation of different physiological functions, and its activity is Ca2 + -dependent (42) . However, iNOS is predominantly involved in the immune regulation and pro-inflammatory response (43, 44) . L-arginine is a substrate of Arg and iNOS, therefore, high expression levels of Arg may deplete L-arginine and increase levels of ornithine and polyamines, which are required for the proliferation of cells and parasites. A reduction in L-arginine causes a decrease in NO through the iNOS pathway (11) . The competition between Arg and iNOS is pivotal in the immune response to infection and determines the course of infection. For example, the peritoneal macrophages in rats differ from those in mice by being resistant to Toxoplasma gondi infection in nature. This resistance has been ascribed to the increased expression and activity of iNOS and, reduced activity of Arg I in rat peritoneal macrophages, compared with mouse peritoneal macrophages (12) . HIV infection significantly reduces the number of CD4 + T cells, particularly in the AIDS phase, and as polyamine, which is the metabolic product of L-arginine by Arg, is an essential substrate for cell proliferation, increased Arg I in the peripheral blood and LNs can increase the number of CD4 + T cells following HIV infection (11) . The results of the present study indicated the negative correlation between the expression of Arg I in peripheral T cells and LNs and peripheral CD4 + T cell count, suggesting that the expression of Arg I increased to compensate for the reduction in CD4 + T cells. However, L-arginine regulates the transcription of iNOS in a concentration-dependent manner (39) and Arg significantly reduces the levels of L-arginine, leading to reduction in iNOS synthesis. Thus, the increase in the expression levels This Arg-induced reduction in iNOS synthesis leads to a reduction in the production of NO, and this release of NO by macrophages is important role in innate immunity (11) .