Characterization of immunosuppressive functions of murine peritoneal macrophages induced with various agents

Abstract

Murine peritoneal macrophages (M phi s), induced with stimuli such as thioglycollate, zymosan A, OK-432, bacille Calmette-Guérin (BCG), or live Mycobacterium intracellulare, showed varying levels of inhibitory activity against the concanavalin A (Con A) blastogenic response of splenic T cells. All test M phi s significantly inhibited the interleukin 2 (IL-2)-producing ability of T cells but this inhibition was not enough to explain the observed reduction in T cell Con A mitogenesis. In contrast, they markedly inhibited IL-2-reactive T cell generation, and the inhibition was sufficient to cause the reduction in T cell mitogenesis. A general relationship was observed between immunosuppressive activity of a given M phi and its active oxygen-producing ability (measured in terms of chemiluminescence) in response to phorbol myristate acetate triggering (r = .84, P less than .005). However, the suppressor activity of test M phi s was not reduced by superoxide dismutase and catalase, indicating that active oxygen radicals themselves did not mediate the expression of the immunosuppressive activity of these M phi s. On the other ahnd, indomethacin (an inhibitor of prostaglandin synthesis) caused a partial reduction in their immunosuppressive activity. The suppressor activity of M phi s induced with intraperitoneal injection of recombinant interferon gamma (IFN-gamma) was markedly reduced in the presence of myoglobin, a scavenger for nitric oxide radical (NO.). Tumor necrosis factor alpha (TNF alpha) failed to affect Con A mitogenesis of splenic T cells, even in combination with IFN-gamma. On the other hand, unsaturated long-chain fatty acids including oleic, linoleic, linolenic, and arachidonic acids markedly reduced the T cell function. These findings suggest some important roles of prostaglandins, NO., and long-chain unsaturated fatty acids as mediators of the expression of immunosuppressive function of the peritoneal M phi s.

Phospholipids and reactive nitrogen intermediates collaborate in expression of the T cell mitogenesis-inhibitory activity of immunosuppressive macrophages induced in mycobacterial infection

“…Previously, we found suppressive activity of free fatty acids including oleic, linoleic, linolenic, and arachidonic acids against SPC blastogenesis [7]. The present study also showed that PS and PI displayed a potent inhibitory activity against Con A-induced SPC blastogenesis.…”

“…It has been also reported by Rockett et al [13] that the reduction of Con A mitogenic response observed in the case of SPC from Plasmodium vinickei-infected mice was restored by the addition of NMMA (a specific inhibitor of NO synthase) [9], thereby indicating the role of NO in the suppression of T cell proliferation induced by malaria parasites. In addition, we previously found that ferrous myoglobin, a scavenger of NO [14], partly overcame the suppressive activity of MAIC-induced macrophages [7], thereby suggesting participation of NO in the immunosuppressive activity of MAIC-induced macrophages. As shown in Table 3, NMMA attenuated in part the suppressive activity of MAIC-induced macrophages (P < 0 : 01; Student's t-test).…”

“…IL-2 production of splenic T cells IL-2 producing activity of Con A-activated SPC was assayed as previously described [7]. Briefly, the 24-h culture fluid harvested from the above SPC culture of Con A mitogenesis was measured for IL-2 activity in terms of the proliferative response of IL-2 dependent cytotoxic T cell line, CTLL-2.…”

“…infection with MAIC, and that they possessed potent suppressive activity against concanavalin A (Con A)-induced mitogenesis of splenocytes (SPCs) [5,6]. Concerning the mediator molecules of the splenic macrophages, the following has been elucidated [5][6][7].…”

Superoxide Prevents Nitric Oxide-Mediated Suppression of Helper T Lymphocytes: Decreased Autoimmune Encephalomyelitis in Nicotinamide Adenine Dinucleotide Phosphate Oxidase Knockout Mice

“…NO may be involved in protection against cytokine-induced systemic damage (18), as well as inhibition of leukocyte adhesion and migration through the endothelial cell layer (19). In addition, NO has been implicated as a major macrophage-derived immunosuppressive factor for T cell immunity (20,21). NO functions as a powerful inhibitor of T cell proliferation (22,23) and also inhibits NF-B activation (24).…”