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1.
The in vitro effect of histamine and its antagonists, cimetidine and clemastine fumarate, on natural killer (NK) and antibody-dependent cellular Cytotoxicity (ADCC) activities of human lymphocytes was investigated. The histamine 1 (H1) antagonist, clemastine fumarate, and the histamine 2 (H2) antagonist, cimetidine, but not histamine alone, inhibited the NK and ADCC activities of lymphocytes when added directly to the mixture of effector and target cells in a 51Cr-release assay. This inhibition was proportional to the concentration of drugs added and was observed at various effector to target ratios against several targets. H1 and H2 antagonists also inhibited NK activities of T cells as well as Percoll-separated, NK-enriched effector cells. The inhibition was significantly reversed by histamine. In target binding assays, clemastine fumarate and cimetidine also decreased the target binding capacity of effector lymphocytes. Further, PBL precultured with histamine (10?3–10?4M) for 24 hr showed a significant decrease in their NK and ADCC activities. In coculture experiments, PBL precultured with histamine suppressed the NK activity of normal autologous effector lymphocytes. PBL precultured with histamine showed an increased number of OKT8+ cells, as estimated using monoclonal antibodies. The suppression of Cytotoxicity was not due to either direct toxicity, steric hindrance, crowding, or cell death, but by functionally viable suppressor cells. An immunoregulatory role for histamine in NK and ADCC reactions is proposed. 相似文献
2.
Ross E. Rocklin Jacqueline Breard Sudhir Gupta Robert A. Good Kenneth L. Melmon 《Cellular immunology》1980,51(2):226-237
The cells which elaborate a soluble suppressor factor in vitro in response to histamine (histamine-induced suppressor factor or HSF) were partially characterized in the present studies. Human blood T- and B-cell populations were purified by affinity chromatography with rabbit anti-human F(Ab′)2 and examined for their ability to make HSF. Highly purified populations of T cells, but not B cells, produced HSF in response to varying concentrations of histamine (10?4 to 10?4M). The HSF-producing cells were characterized further by means of affinity chromatography with columns containing conjugates of insolubilized histamine as well as by rosette formation with IgG (Tγ)- or IgM (Tμ)-coated ox red blood cells. These studies revealed the following: (a) Cells that synthesize HSF are retained on histamine (but not control) columns; (b) cells with histamine receptors comprise approximately 50% of the Tγ subpopulation but are not found in the Tμ subpopulation; (c) cells not retained by histamine columns have a reduced capacity to develop into suppressor cells following stimulation by concanavalin A or specific antigen (compared to unfractionated or control column passed cells). In addition, it was shown that cells synthesizing HSF predominantly express histamine type 2 receptors: (d)4-Methyl histamine (H2 agonist), but not 2-methyl histamine (H1 agonist), was capable of inducing HSF production; (e) cimetidine (H2 antagonist) inhibited HSF production but chlorpheniramine (H1 antagonist) did not. Taken together, these experiments suggest that T lymphocytes capable of expressing suppressor function following activation by histamine, specific antigen, concanavalin A, or perhaps through their Fc receptors may either be heterogeneous within the same subpopulation or more likely be the same cell with the complement of receptors described above. 相似文献
3.
R E Rocklin 《Journal of immunology (Baltimore, Md. : 1950)》1977,118(5):1734-1738
Histamine added in vitro to cultures of sensitized lymphocytes suppresses antigen-induced production of migration inhibitory factor (MIF) and proliferation by these cells. Recent studies have suggested that lymphocytes bearing histamine type-2 receptors play a regulatory role in these in vitro responses. The present studies were undertaken to determine if suppressor function by cells having histamine receptors was mediated through a soluble product. It was found that lymph node cells from nonimmune or immune strain 2 guinea pigs elaborate a nondialyzable factor into the culture supernatant when incubated with 10(-3) to 10(-5) M histamine (histamine-induced suppressor factor of HSF). HSF, when cocultured with sensitized lymphocytes, suppressed their MIF and proliferative responses to antigen. HSF was made by lymphocytes but not macrophages. Its production could be blocked by an H2 receptor antagonist (burimamide) but not an H1 receptor antagonist (chlorpheniramine). Furthermore, the inhibitory effect of HSF was reversible as lymphocytes washed free of the factor after 24 hr and recultured with fresh medium and antigen were able to produce MIF. Gel filtration by Sephadex G-100 chromatography indicated that HSF had an approximate m.w. of 23,000 to 40,000. These results suggest that the release of histamine at the sites of immediate hypersensitivity reactions, possibly by generating HSF activity, may play a regulatory role in the subsequent development of cellular-immune reactions at the same site. 相似文献
4.
Mechanism of histamine-induced inhibition of lymphocyte response to mitogens in mice 总被引:3,自引:0,他引:3
Histamine induced, in mice, an inhibition of lymphocyte response to PHA and LPS, at molar concentrations ranging from 10?3 to 10?9M. This inhibition occurs as a specific interaction between histamine and T lymphocytes bearing H2-type receptors for this hormone (H + cells) and Ly 2 membrane antigens. Two features of the suppressive activity of this T-cell subpopulation were observed: (i) when histamine is added at the beginning of the culture period with PHA or LPS, it activates the suppressor activity of H + cells which act on the lymphocyte population responding to PHA and LPS; (ii) preincubation of spleen lymphocytes with histamine for 24 hr induces suppressor cells which inhibit the response to PHA, but not to LPS, of syngeneic lymphocytes in a coculture system, and which are radiosensitive. The role of PHA as a second stimulus of histamine-induced suppressor cells, and the relation between these cells and PHA or Con A-induced suppressor cells, are discussed. 相似文献
5.
Glass adherent splenic T cells, cultured in the presence of prostaglandin E2 (10?5M), were found to elicit a factor capable of nonspecifically suppressing PHA- and LPS-induced mitogenesis. Cells from C57B1/6J, Balb/C, and C3H/He mice were all capable of producing this suppressor factor, although some degree of variability in the response of cells from C3H mice to the factor was observed. The suppressor (designated prostaglandin-induced T-cell derived suppressor, PITS) was characterized biochemically and it was found that the activity was resistant to boiling, and treatment with RNase and DNase, yet was sensitive to treatment with proteinase K, trypsin, and Pronase. Further, PITS supernatants were found to contain at least two suppressors with approximate molecular weights of 35,000 (PITSα) and 5000 (PITSβ). Results from experiments with cycloheximide-treated glass-adherent T cells indicate that prostaglandin E2 may function by inducing the release rather than de novo synthesis of the PITS. These results indicate that the reported overall suppressive effect of prostaglandin E2 on lymphocytes may in part be due to the release by certain T cells of a suppressive factor. 相似文献
6.
Exogenously added histamine in non-cytotoxic concentrations (10?5?10?3M) suppresses in vitro proliferation of lymphocytes induced by PHA or Concanavalin A. This suppressive effect was observed when histamine was present for as short as hr in the beginning of the culture. Histamine, in concentrations as high as 10?3M, did not cause increased release of isotope from 51Cr-labeled lymphocytes following 4 hr of incubation. The histamine H2 receptor antagonist, metiamide, but not the H1 receptor antagonists diphenhydramine or chlorpheniramine, blocked the histamine suppressive effect. Some of the biological implications of these findings are discussed. 相似文献
7.
M P Nair J M Cilik S A Schwartz 《Journal of immunology (Baltimore, Md. : 1950)》1986,136(7):2456-2462
Culture supernatants of lymphocytes stimulated with 10(-3) to 10(-8) M histamine contain histamine-induced soluble suppressor factor (HISSF) that significantly inhibits the natural killer (NK) cell functions of allogeneic lymphocytes. Lymphocytes precultured with increasing concentrations of HISSF showed a dose-dependent suppressive effect on their NK activity. HISSF was not cytotoxic itself and produced suppressive effects on PBL, NK-enriched large granular lymphocytes (LGL), and isolated T cells. Suppression was evident throughout a range of effector:target cell ratios. Production of HISSF was specifically blocked by the H2 antagonist cimetidine, but not by the H1 antagonist clemastine fumarate. Furthermore, H1 and H2 antagonists themselves do not induce production of HISSF. Although HISSF could inhibit the cytotoxicity of LGL, LGL themselves do not produce HISSF. HISSF inhibition of NK activity could be completely reversed by treating effector lymphocytes with recombinant interferon-alpha (IFN) for 1 or 2 hr or culturing them with purified interleukin 2(IL 2) for 36 hr. Our data suggest that exogenous IFN and IL 2 may have therapeutic potential in the treatment of immunological diseases associated with histamine-induced suppressor cell activity. 相似文献
8.
T lymphocytes were isolated from the spleens, thymuses, and bone marrow of three inbred mice strains, and the effects of two carcinogenic polycyclic aromatic hydrocarbons (PAH) on the mitogen activation of these cells were assessed. Benzanthracene (BA) and 3-methylcholanthrene (MCA) enhanced mitogen activation of splenic T cells in a strain-related fashion: C3H greater than C57BL greater than DBA/2 (P less than 0.025). This pattern of strain relatedness was not observed in T cells from the other lymphoid organs. Mitogen activation was suppressed by histamine to a greater degree in T cells from PAH-responsive mice (C3H and C57BL) than in the nonresponsive strain (DBA/2). Histamine inhibited rosette formation between T cells and histamine-conjugated sheep red blood cells. A histamine suppressor factor (HSF), isolated from splenic lymphocytes grown in the presence of histamine or histamine plus MCA, was significantly higher in activity in culture supernatants from T cells derived from responsive mice than from nonresponsive mice. With the use of Lyt 1 and Lyt 2 monoclonal antibodies, it is shown that the baseline percentage of T helper and T suppressor cells was not significantly different in all three strains. Further, histamine and MCA had no effect on the expression of the Lyt 1 and Lyt 2 surface antigens on splenic lymphocytes. These results suggest that PAH-responsive mice may have more T-cell H2 receptors than T cells from nonresponsive mice. Histamine and PAH compounds may act on the same T-cell subsets, as evidenced by the fact that BA and MCA enhance blastogenesis, histamine suppresses mitogen activation, and these PAH compounds enhance histamine and HSF activity. 相似文献
9.
M M Khan K L Melmon C G Fathman B Hertel-Wulff S Strober 《Journal of immunology (Baltimore, Md. : 1950)》1985,134(6):4100-4106
The pharmacologic effects of histamine and isoproterenol (autacoids) were studied on clones of murine T helper (TH) and natural suppressor (NS) cells. The data are consistent with receptors for the autacoids being nonrandomly distributed on phenotypically and functionally distinct clones. The effects of histamine on IL 2 secretion by TH cells could be either inhibitory or stimulatory, depending on the conditions of incubation with the autacoid. When TH cells were pretreated with histamine, their secretion of IL 2 was augmented; conversely, if histamine was added to the TH cells in the presence of antigen, IL 2 secretion was inhibited. The suppressor function of NS cells was enhanced by preincubation with histamine (10(-4) M) for 4 hr before the washed NS cells were added to responder and stimulator cells in mixed lymphocyte cultures. Two H1 receptor antagonists, mepyramine (10(-6) M) and pyrobutamine (10(-7) M), each competitively blocked the histamine activation of the NS cells, but an H2 receptor antagonist cimetidine (10(-5) M) did not alter the suppressor-enhancing function of histamine. Activation of NS cells did not occur if histamine was added with responder, stimulator, and co-cultured cells in MLR. The effects of each autacoid were additive in cytolytic T cells alone. The adenylate cyclase pools that can be stimulated by isoproterenol and histamine in cytolytic T cells may be independent of each other, but further work will be needed to prove this point. 相似文献
10.
Differential sensitivity of T suppressor cell expression to inhibition by histamine type 2 receptor antagonists 总被引:1,自引:0,他引:1
D E Griswold S Alessi A M Badger G Poste N Hanna 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(6):1811-1815
The ability of the histamine type 2 (H2) receptor antagonists cimetidine and oxmetidine to inhibit the immune suppression mediated by different types of murine T suppressor cells has been evaluated. Both compounds at doses as low as 1 mg/kg administered as a per os (p.o.) twice a day (b.i.d.) regimen abrogated the expression of dinitrobenzene sulfonic acid-induced, Lyt-2+, T suppressor cells and stimulated contact sensitivity to dinitrofluorobenzene in adoptive transfer experiments. Comparable inhibition of Lyt-1+, T suppressor cell activity induced by UV irradiation required higher doses of cimetidine and oxmetidine (200 and 25 mg/kg; p.o., b.i.d., respectively). In contrast, the T suppressor cell-mediated unresponsiveness induced by inoculation with a high dose of sheep red blood cells was refractory to treatment in vivo with either cimetidine or oxmetidine regardless of the dose. These results indicate that T suppressor cell populations differ markedly in their susceptibility to modulation by H2 antagonists. The histamine type 1 (H1) receptor antagonist diphenhydramine, had no effect on suppressor cell activity in any of these systems, indicating that modulation of suppressor cell activity is mediated through an H2 receptor interaction. 相似文献
11.
Vineesh V. Raveendran Donald D. Smith Xiaoyu Tan Matthew E. Sweeney Gregory A. Reed Colleen A. Flynn Ossama W. Tawfik Ginger Milne Kottarappat N. Dileepan 《PloS one》2014,9(7)
Although increased serum histamine levels and H1R expression in the plaque are seen in atherosclerosis, it is not known whether H1R activation is a causative factor in the development of the disease, or is a host defense response to atherogenic signals. In order to elucidate how pharmacological inhibition of histamine receptor 1 (H1R) signaling affects atherogenesis, we administered either cetirizine (1 and 4 mg/kg. b.w) or fexofenadine (10 and 40 mg/kg. b.w) to ApoE−/− mice maintained on a high fat diet for three months. Mice ingesting a low dose of cetirizine or fexofenadine had significantly higher plaque coverage in the aorta and cross-sectional lesion area at the aortic root. Surprisingly, the higher doses of cetirizine or fexofenadine did not enhance atherosclerotic lesion coverage over the controls. The low dose of fexofenadine, but not cetirizine, increased serum LDL cholesterol. Interestingly, the expression of iNOS and eNOS mRNA was increased in aortas of mice on high doses of cetirizine or fexofenadine. This may be a compensatory nitric oxide (NO)-mediated vasodilatory mechanism that accounts for the lack of increase in the progression of atherosclerosis. Although the administration of cetirizine did not alter blood pressure between the groups, there was a positive correlation between blood pressure and lesion/media ratio at the aortic root in mice receiving the low dose of cetirizine. However, this association was not observed in mice treated with the high dose of cetirizine or either doses of fexofenadine. The macrophages or T lymphocytes densities were not altered by low doses of H1-antihistamines, whereas, high doses decreased the number of macrophages but not T lymphocytes. The number of mast cells was decreased only in mice treated with low dose of fexofenadine. These results demonstrate that chronic ingestion of low therapeutic doses of cetirizine or fexofenadine enhance progression of atherosclerosis. 相似文献
12.
Guinea pig lymphocytes are stimulated by histamine to produce a soluble factor with immunosuppressive properties. This factor, termed histamine-induced suppressor factor or HSF, abrogates the production of migration inhibitory factor (MIF) and proliferative response to specific antigen. In the present study we have determined the lymphocyte subpopulation which elaborates HSF, the lymphoid tissue source, the kinetics of its generation in relation to immunization, and the nature of the histamine receptor involved in modification of the release of HSF. HSF activity could be detected in populations of cells from spleen and lymph nodes prior to active immunization of the donor, but not in cells from the donor's blood or thymus. Following immunization with ortho-chloro benzoyl-bovine γ-globulin in complete Freund's adjuvant (CFA), more HSF activity was detected in cells from the donor's spleen and lymph nodes. The peak response was seen 2 weeks postimmunization when significant amounts of HSF also were made by cells from the blood and thymus. Concentrations of T-cell-enriched and B-cell-enriched populations were tested for their ability to make HSF. We found that T-cell-enriched, but not B-cell-enriched populations, made significant amounts of HSF. Cells from the lymph nodes of immunized donors were chromatographed over affinity columns made of insolubilized conjugates of histamine with albumin. The nonretained cells were unable to generate HSF, whereas HSF activity was detected in the cells that were retained by the columns. This finding strongly suggests that the HSF-producing cells have receptors for histamine. Cells from CFA-immune lymph nodes were incubated with H1 (2-methyl histamine) and H2 (4-methyl histamine) agonists to determine their relative potency and, therefore, the nature of the histamine receptors on these cells that were modifying HSF release. Although both agonists could induce generation of HSF when high concentrations (10?3M) were used, only the H2 agonist stimulated production or release of HSF at lower concentrations (10?5M). These HSF-producing cells appear to be selectively sensitive to H2 agonists and likely have a predominance of H2 receptors. Allergic mediators other than histamine were studied to determine their ability to allow elaboration of HSF-like activity from CFA-immune lymph node cells. Serotonin (10?3M), slow-reacting substance of anaphylaxis (100 units/ml), eosinophil chemotactic factor (tetrapeptide; 10?5M), and prostaglandin E1 (10?4M) were unable to induce HSF-like activity in lymph node cells from donors immunized with CFA. Furthermore, other agents which raise intracellular levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) such as isoproterenol and cholera toxin, as well as the dibutyryl form of cyclic AMP itself, were also unable to generate HSF-like activity. Thus, histamine is unique among the allergic mediators in stimulating elaboration of the suppressive substance. These findings also suggest that the ability of histamine to stimulate HSF may not reside in the conventional pathway linked to cAMP accumulation, but rather to an as yet undefined pathway of cell activation. A model is presented which further implicates histamine as a modulator of cellular immune reactions. 相似文献
13.
Human cytolytic T lymphocytes (CTL) were generated in the presence and absence of histamine in order to define the role of this autacoid in immune regulation. Histamine (10(-8)-10(-4) M) suppressed the generation of class I specific CTL but, at 10(-4) M, actually increased class II specific cytolysis. Histamine acted at the level of CTL generation; histamine was not present in the cytolytic assay. When histamine was added to the cytolytic assay with CTL grown without histamine, the lytic ability of the effector cells was similar to that of controls. Histamine-induced suppression of class I specific cytolysis was blocked by continuous culture with the H2 antagonist ranitidine but not with the H1 antagonist pyrilamine. These data suggest that suppression was mediated by the H2 receptor. Continuous culture with histamine had no effect on T cell proliferation or the expression of cell surface molecules. Histamine-induced suppression of class I specific cytolysis was reversed by the addition of PHA to the cytotoxicity assay, showing that the cytolytic machinery was intact. These data provide evidence that histamine is involved in regulation of cytolytic T cells. 相似文献
14.
When soluble histamine is added to guinea pig lymphocytes in vitro, antigen-induced cellular proliferation and the production of migration inhibitory factor is suppressed. The inhibitory effects that are produced by histamine have been shown to be mediated by the histamine-type 2 receptors of the involved cells, but the exact nature of this suppression has not been fully explored. The present studies have evaluated, following immunization, the effect of histamine on macrophage function in vitro, and affinity chromatography to delete a subpopulation of cells bearing histamine receptors. When we treated monolayers of peritoneal exudate cells with histamine (up to 10?3M) we found that histamine did not interfere with antigen binding by macrophages, macro phage presentation of antigen to lymphocytes, nor the antigen-independent or antigen-dependent lymphocyte-macrophage rosetting. Columns containing insolubilized conjugates of histamine and rabbit serum albumin depleted a subpopulation of cells responsive to histamine i.e., the non-adherent cells made migration inhibitory factor and proliferated in the presence of histamine. The latter finding suggested that the retained cells might have suppressor function and if so, might mediate their effect through the release of a soluble factor. Preliminary data obtained in these studies supports this hypothesis. We conclude that cells bearing histamine receptors may serve a regulatory role in cellular immunity after their activation by histamine by producing a non-dialyzable factor with immunosuppressive properties. 相似文献
15.
Ross E. Rocklin Ilze Klselis Dennis J. Beer Paulo Rossi Franco Maggi Joseph A. Bellanti 《Cellular immunology》1983,77(1):92-98
A possible mechanism to explain the suppression of mitogen-induced lymphocyte proliferation in vitro by histamine-stimulated mononuclear cells was investigated. In initial experiments, the inhibitory action of histamine-induced suppressor factor (HSF) on lymphocyte proliferation was documented to be reduced by the addition of indomethacin (1 μg/ml). Moreover, the addition of exogeneous PGE2 (10?7-10?8 M) to mononuclear cell cultures reconstituted HSF activity in the presence of indomethacin. In order to ascertain the nature of the target cell responding to HSF, control and suppressor supernatants were incubated with human lymphocytes or monocytes (5 × 106 cells/ml) for 24 hr. Following incubation, the supernatants were assayed for their content of prostaglandin E2, F2α, and thromboxane B2. Monocytes (but not lymphocytes) incubated with supernatants containing HSF increased their production of prostaglandin E2, F2α, and thromboxane B2 by 169, 53, and 49%, respectively. Suppressor supernatants were generated with histamine or an H-2 agonist (dimaprit) and chromatographed by gel filtration on Sephadex G-100. The elution profiles for the factor(s) inducing suppression of lymphocyte proliferation (25–40,000 daltons) and augmenting PGE2 production (25,000 daltons) overlapped but were not identical. Collectively, these data suggest that HSF-mediated inhibition of lymphocyte proliferation may occur in part through the augmented production of prostaglandins and/or thromboxane B2 by human monocytes. 相似文献
16.
Is prostaglandin a mediator for the inhibitory action of histamine,hydrocortisone, and isoproterenol? 总被引:1,自引:0,他引:1
We examined the inhibitory actions of prostaglandin E2, histamine, isoproterenol, hydrocortisone, and interferon on lymphocyte mitogenesis. There was a high degree of intercorrelation between the amount of inhibition caused by prostaglandin E2, histamine, isoproterenol, and hydrocortisone, but not interferon, in any given subject; that is if lymphocytes from a given subject were highly sensitive to inhibition by one of those agents, they were also sensitive to the other agents. The inhibitory actions of histamine, isoproterenol, or hydrocortisone could be partially blocked by adding prostaglandin synthetase inhibitors to the mitogen cultures. Preincubation of the lymphocytes for 18 hr prior to the addition of mitogens and inhibitors resulted in a loss in sensitivity to the inhibitors other than interferon. Removal of glass-adherent cells (the prostaglandin-producing cells) prior to culture lessened the inhibition caused by histamine and isoproterenol. The above data would suggest that these inhibitors may act via prostaglandin; however, all of these compounds actually decrease prostaglandin production in cultures of peripheral blood mononuclear cells. The implications of these findings are discussed. 相似文献
17.
Rapakinin, Arg-Ile-Tyr, is a vasorelaxing, anti-hypertensive and anorexigenic peptide derived from rapeseed napin. In this study, we found that rapakinin intracerebroventricularly administered to mice inhibited the analgesic effect of morphine, evaluated by the tail-pinch test. The anti-opioid activity of rapakinin was blocked by LY225910, an antagonist of the cholecystokinin (CCK) CCK2 receptor, but not by lorglumide, an antagonist of the CCK1 receptor. The anti-opioid activity of rapakinin was also blocked by CAY10441, an antagonist of the prostaglandin (PG) IP receptor. These results suggest that the anti-opioid activity of rapakinin is mediated by the CCK2 and IP receptors. The anti-opioid activity induced by ciprostene, an IP receptor agonist, was blocked by LY225910, while that of CCK-8 was not blocked by CAY10441. Thus, it is demonstrated that the CCK-CCK2 system was activated downstream of the PGI2-IP receptor system. Taken together, rapakinin shows anti-opioid activity via the activation of the PGI2-IP receptor system followed by the CCK-CCK2 receptor system. 相似文献
18.
Control of mitogen-induced transformation: characterization of a splenic suppressor cell and its mode of action. 总被引:4,自引:0,他引:4
The present study demonstrates that mouse spleen cells contain a population of glass wool adherent T lymphocytes which exhibit the capacity to suppress non-glass adherent lymphocyte responses to mitogens. These suppressor cells are stimulated by both low and high doses of PHA1 and high doses of con A. The suppressor cell effect is observed when UNA, but not RNA or protein synthesis, is studied. This glass-adherent suppressor cell population is characterized as being the primary DNA synthesizing cells during the early (0–8 hr) stages of culture. Suppression still occurs when the suppressor cells are treated with mitomycin C, actinomycin D or cycloheximide. This implies that new macromolecular synthesis may not be required for suppression to occur. Suppression is blocked by inhibiting synthesis of prostaglandin and is mimicked by Bu2cAMP. This suggests that mitogen activated suppressor cells regulate T cell responses via production of prostaglandin which modulates the concentration of intracellular cyclic nucleotide levels. 相似文献
19.
J V Weinstock S W Chensue D L Boros 《Journal of immunology (Baltimore, Md. : 1950)》1983,130(1):423-427
The possible role of histamine and histamine-receptored inflammatory cells in the granulomatous response of Schistosoma mansoni-infected mice was examined. Special staining revealed the presence of numerous mast cells, many partially degranulated within the liver granulomas. Treatment of infected mice with cimetidine (an H2 receptor antagonist) enhanced, and diphenyhydramine (an H1 receptor antagonist) decreased the granulomatous response. Fluorescein-labeled histamine-rabbit serum albumin conjugate (H-FRSA) and unlabeled conjugate (H-RSA)-coated culture plates were used to identify and isolate cells with histamine receptors. A large proportion of granuloma macrophages, lymphocytes, eosinophils, neutrophils, and splenic lymphocytes had histamine receptors. Elution of adherent cells from H-RSA-coated culture plates with H1 or H2 receptor antagonists suggested that receptors on granuloma cells were predominately H1 with some granuloma lymphocytes bearing H2-type receptors. Splenic lymphocytes from infected mice were functionally divided according to the presence or absence of histamine receptors on their cell surface. Receptor-negative lymphocytes appeared to mediate SEA-stimulated MIF production (TDH cells) and participated in the adoptive transfer of suppression of granulomas (TH cells). Whereas, TS cells appeared to have histamine receptors. Based on these data, it is inferred that lymphocytes that regulate lymphokine production (TS cells) within the granuloma may be triggered via their histamine receptors to exert suppressive activity. 相似文献
20.
《Cytokine》2015,72(2):145-153
Since clinical application of MSCs requires long-term ex vivo culture inducing senescence in MSCs and reducing the therapeutic activity of transplanted MSCs, numerous efforts have been attempted to sustain the active state of MSCs. Substance P (SP) is a neuropeptide that functions to activate the cellular physiological responses of MSCs, including proliferation, migration, and secretion of specific cytokines. In this study, we explored the potential of SP to restore the weakened immune modulating activity of MSCs resulting from long-term culture by measuring T cell activity and interleukin-2 (IL-2) secretion of CD4+ Jurkat leukemic T cells and primary CD4+ T cells. As the number of cell passages increased, the immunosuppressive function of MSCs based on T cell activity decreased. This weakened activity of MSCs could be restored by SP treatment and nullified by co-treatment of an NK1 receptor blocker. Higher levels of transforming growth factor beta 1 (TGF-β1) secretion were noted in the medium of SP-treated late passage MSC cultures, but IL-10 levels did not change. SP-treated MSC-conditioned medium decreased T cell activity and IL-2/Interferon gamma (IFN-g) secretion in T cells even in the activation by lipopolysaccharide (LPS) or CD3/CD28 antibodies, both of which were successfully blocked by inhibiting the TGF beta signaling pathway. This stimulatory effect of SP on late passage MSCs was also confirmed in direct cell–cell contact co-culture of MSCs and CD4+ Jurkat T cells. Collectively, our study suggests that SP pretreatment to MSCs may recover the immunosuppressive function of late passage MSCs by potentiating their ability to secrete TGF-β1, which can enhance the therapeutic activity of ex vivo expanded MSCs in long-term culture. 相似文献