Characteristics of immunosuppressive macrophages induced in spleen cells by Mycobacterium avium complex infections in mice

Tomioka, Haruaki; Saito, Hajime; Yamada, Yoshitaka

doi:10.1099/00221287-136-5-965

Cited by 25 publications

(38 citation statements)

References 27 publications

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“…This inhibitory activity was partly attributable to a hydrophobic substance which contained phosphatidylglycerol. Previously we found that the suppressor activity of MAIC-induced macrophages was abrogated by cytochalasin B [5], thereby indicating the essential role of membrane function of these macrophages in the expression of their immunosuppressive activity. This suggests that cell-to-cell interaction is also important in the case of MAICinduced macrophages.…”

Section: Discussionmentioning

confidence: 88%

“…Con A-induced mitogenesis of SPC was measured as reported previously [5]. Briefly, 2 : 5 2 10 5 SPC were cultured in 0 .…”

Section: Mitogenic Response Of Spcmentioning

confidence: 99%

“…First, although MAIC-induced macrophages showed increased ability for active oxygen release, scavengers for oxygen radicals (superoxide dismutase and catalase) could not attenuate the suppressive activity [6]. Therefore, active oxygen intermediates are not involved.…”

Section: Introductionmentioning

confidence: 97%

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

Tomioka¹,

Kishimoto

Maw³

1996

Clinical and Experimental Immunology

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SUMMARYWe studied the role of phospholipids and nitric oxide in expression of the suppressor activity of splenic macrophages induced by Mycobacterium avium-intracellulare complex infection (MAICinduced macrophages) in mice against mitogenic response of concanavalin A (Con A)-stimulated splenocytes (SPC) as follows. First, phosphatidylserine (PS) and phosphatidylinositol were found to suppress Con A-induced mitogenesis of SPC via inhibition of IL-2 production and acquisition of IL-2 reactivity in Con A-stimulated T cells. The mitogenesis-inhibitory activity of PS was increased when SPC were cultured under mildly acidic condition (pH 6 . 3). When SPC were pretreated with PS for 24 h prior to Con A blastogenesis, their mitogenic response was irreversibly abrogated. Second, N G -monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthase, was found to attenuate in part the expression of the suppressor activity of MAIC-induced macrophages. Third, reactive nitrogen intermediates (RNI) including NO generated from acidified NO ÿ 2 exerted potent inhibitory activity against SPC mitogenic response, and the suppressive activity of RNI was significantly augmented by the combination with PS. These findings indicate that phospholipids and RNI play an important role in the expression of suppressor activity of MAIC-induced macrophages as the effector molecules.

show abstract

Section: Discussionmentioning

confidence: 88%

“…Con A-induced mitogenesis of SPC was measured as reported previously [5]. Briefly, 2 : 5 2 10 5 SPC were cultured in 0 .…”

Section: Mitogenic Response Of Spcmentioning

confidence: 99%

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

Tomioka¹,

Kishimoto

Maw³

1996

Clinical and Experimental Immunology

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“…In the absence of pathogens, DCs maintain T cell unresponsiveness by presenting self-Ags without costimulation (2). In addition, M⌽ suppress T cell activity (3). In contrast, pathogen ligation of TLRs activates DCs and M⌽ by inducing costimulatory molecules and promoting cytokine secretion.…”

mentioning

confidence: 99%

“…Dendritic cells (DCs) 3 and macrophages (M⌽) regulate the balance between immunity and tolerance by controlling lymphocyte activation. In the absence of pathogens, DCs maintain T cell unresponsiveness by presenting self-Ags without costimulation (2).…”

mentioning

confidence: 99%

Cutting Edge: Low-Affinity, Smith Antigen-Specific B Cells Are Tolerized by Dendritic Cells and Macrophages

Kilmon

Rutan

Clarke

et al. 2005

The Journal of Immunology

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Polyclonal B cell activation promotes immunity without the loss of tolerance. Our data show that during activation of the innate immune system, B cell tolerance to Smith Ag Sm is maintained by dendritic cells (DCs) and macrophages (MΦ). TLR4-activated myeloid DCs and MΦ, but not plasmacytoid or lymphoid DCs, repressed autoreactive B cells through the secretion of soluble mediators, including IL-6. Although IL-6 promotes plasma cell differentiation of B cells acutely stimulated by Ag, we show that it repressed cells that were chronically exposed to self-Ag. This mechanism of tolerance was not limited to Smith Ag-specific B cells as hen egg lysozyme- and p-azophenylarsonate-specific B cells were similarly affected. Our data define a tolerogenic role for MΦ and DCs in regulating autoreactive B cells during activation of the innate immune system.

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

Tomioka

Saito

1992

Journal of Leukocyte Biology

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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.

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Characteristics of immunosuppressive macrophages induced in spleen cells by Mycobacterium avium complex infections in mice

Cited by 25 publications

References 27 publications

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

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

Cutting Edge: Low-Affinity, Smith Antigen-Specific B Cells Are Tolerized by Dendritic Cells and Macrophages

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

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