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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro lymphocyte proliferative assays were performed using Lewis (Lew) and Brown Norway (BN) rats, and compared to induction of monocyte/macrophage procoagulant activity (PCA) in a mixed lymphocyte culture and by endotoxin (LPS) (E. Coli 0111:B4). Splenic mononuclear cells from Lew rats had significantly greater mitogen-induced proliferation to concanavalin A (P = .002) and phytohemagglutinin (P = 0.007). The Lew cells also showed greater allogeneically induced proliferation by BN cells in a one-way MLC in comparison to the reciprocal BN proliferative response (P less than 0.04). PCA induction in peripheral blood mononuclear cells (PBM) by allogeneic stimulation in MLC or total content PCA by LPS did not vary significantly between the 2 strains (P greater than 0.5). Induction of PCA by LPS was rapid, with a moderate rise over basal activity at 3 hr and maximal activity at 6 hr. Two-way allogeneic induction of PCA in PBM from BN and Lew rats resulted in PCA elevation by 3 hr, which became maximal at 18 hr. One-way MLC with Lew or BN cells as responders resulted in moderate increases in PCA by 3-6 hr, with equivalent maximal activities recorded at 18 hr. Viable PCA accounted for 26-32% of total content PCA in both Lew and BN rats. Maximal allogeneic PCA induction by MLC was 14-18% of PCA induced by LPS and required a longer incubation for its expression. Our results indicate that in vitro PCA expression by Lew and BN PBM following allogeneic or endotoxin stimulation shows little interstrain variability in comparison to lymphocyte proliferative responses. Thus PCA appears to more closely reflect the observed in vivo responses of these strains to allogeneic challenge.
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PMID:Monocyte/macrophage procoagulant activity as a measure of immune responsiveness in Lewis and brown Norway inbred rats. Discordance with lymphocyte proliferative assays. 252 55

A number of species respond to bacterial endotoxin (lipopolysaccharide [LPS]) wherein cells of the monocyte-macrophage lineage are rapidly induced either directly or via T-cell collaboration to initiate the extrinsic coagulation protease pathway. This results in fibrin formation and deposition as well as consumption of plasma coagulation proteins. It has been claimed that this cellular response, basic to the Shwartzman reaction, is lacking in rats and may account for the more limited severity of the Shwartzman reaction in this species. We examined the in vitro lymphoid procoagulant response in Fischer 344, Brown Norway, and Lewis rats. When peripheral blood mononuclear cells (PBM) were stimulated in vitro with LPS, a procoagulant activity (PCA) response was observed when assayed by acceleration of clotting of recalcified human or rat platelet-poor plasma. The response was rapid, with a maximum achieved at 4 h. PCA was not physically dissociated from viable PBM by 5 mM EDTA, which is consistent with the presence of an intrinsic plasma membrane initiator molecule rather than calcium-bound gamma-carboxylated glutamic acid-containing proteases. The induction of monocyte PCA was prevented by incubation of cells with cycloheximide or actinomycin D, implicating a new biosynthetic requirement. Cultivation of PBM with warfarin did not diminish the function of the effector PCA, nor did vitamin K augment the function of the endotoxin-induced PCA, indicating that the functional activity was not attributable to gamma-carboxylated glutamic acid-containing proteins. No inhibition of the cellular PCA molecule was produced by serine protease inhibitors. The LPS-induced PCA appeared to involve a tissue factor-like molecule since both factors X and VII were required in mediating PCA. Isolation of monocytes and T lymphocytes from LPS-stimulated PBM demonstrated that PCA was present in the monocyte-rich fraction. When isolated rat T lymphocytes and monocytes were separately exposed to LPS, PCA was not induced. In contrast, when the cells were combined, LPS induced PCA, indicating that the PCA response involved cellular collaboration between cells present in T lymphocyte and monocyte populations.
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PMID:Lymphoid procoagulant response to bacterial endotoxin in the rat. 384 Jul 72

Lipopolysaccharide from a smooth strain of Salmonella minnesota was fractionated into two major fractions and one intermediate fraction by using sodium dodecylsulfate-polyacrylamide gel electrophoresis. On the basis of the study by Hitchcock and Brown, it was deduced that the top fraction was mainly long O-side chain LPS and the bottom fraction was O-side chain-less LPS. The middle fraction was a mixture of both short O-side chain LPS and O-side chain-less LPS. The antigenic properties and biological activities were not altered in this fractionation procedure. Comparison of the biological activities of the top fraction with those of the bottom fraction revealed that the bottom fraction had higher activity in polyclonal B-cell activation and spleen-swelling effect and that there was no significant difference in adjuvant activity, ability to render macrophages cytotoxic, induction of colony-stimulating factor and the ability to induce the Schwartzmann reaction. It was suggested that O-side chain makes no contribution to the latter biological activities including adjuvant activity of S. minnesota LPS.
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PMID:Biological activities of lipopolysaccharide fractionated by preparative acrylamide gel electrophoresis. 387 89

Spleen cells of two rat strains, Lewis and Brown Norway (BN), have been activated by lectins and by antibodies specific for immunoglobulin isotypes embedded in their cell membranes. Optimal concentrations of antibodies specific for mu, gamma, or delta-chains of rat augments in vitro incorporation of 3H-TdR 5 to 18-fold in Lewis B lymphocytes and 1.5 to 4-fold in BN B lymphocytes. In addition, F(ab')2 fragments of anti-Ig reagents induced Lewis splenic B cells but not BN B cells to incorporate 3H-TdR. Responses to LPS and dextran sulfate, B lymphocyte mitogens, measured by radioactive uptake, were five to 10 times greater in Lewis B cell populations than in BN B cell populations. Density of surface Ig isotypes and capping kinetics were similar in the two rat strains, although the percentage of T cells, T cell subsets, B cells, and Ia+ B cells differed in the spleens of these strains of rats. Both T lymphocytes and macrophages were needed in culture to effect an optimal response. IL-2 restored the response in B cell cultures depleted of T cells and macrophages, and enhanced 3H-TdR uptake in whole spleen cells of Lewis but not BN rats. The strain-dependent responsiveness of B cells to specific anti-Ig reagents or B cell mitogens appears to be associated with inherent (genetic) defects in T cells and B cells or defects in T cell to B cell cooperation in BN rats.
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PMID:Activation of rat B lymphocytes. I. Characterization of anti-immunoglobulin responses and isotype density of rat B cells. 679 18

Tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) modulate immune responses, as TNF is postulated as a first messenger for priming immune cells and IFN as the second messenger for activation. Nitric oxide (NO) is also an important mediator of immune function, as NO produced by immune cells in response to cytokines such as TNF and IFN may be a cytotoxic end-product effector of immune activation. To examine TNF and IFN modulation of NO production and effects upon allograft survival, we studied the in vitro effect of TNF, IFN, and lipopolysaccharide (LPS, as a nonspecific immune stimulator and TNF promoter) singly or together on NO production in unstimulated rat splenocytes or in response to allogeneic stimulation in MHC mismatch (Brown-Norway, BN, vs Lewis, LEW) mixed lymphocyte reactions. Nitrite as a stable reaction product of NO was determined by a colorimetric method based on the Griess reaction. Interestingly, unstimulated cells had little NO production in response to TNF or IFN; however, following nonspecific (LPS) or allogeneic stimulation there was a significant upregulation of NO production that was synergistically enhanced by the presence of both TNF and IFN. Significantly, anti-TNF antibody inhibited NO production up to 60% in all groups. In vivo studies used a cardiac heterotopic allotransplant model, again BN to LEW. Control recipients received no immunotherapy. Experimental recipients received IFN alone, anti-IFN antibody, anti-TNF antibody, or anti-TNF and anti-IFN antibody. Results from these allograft experiments showed no influence on survival by IFN alone or anti-IFN antibody alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor-alpha and interferon-gamma modulation of nitric oxide and allograft survival. 763 Jan 11

The results described herein indicate that elevation of IL-1 in rat brain, either by infusion of IL-1 into the brain or by stimulation of release of endogenous IL-1 in the brain by LPS, rapidly suppresses a variety of immune responses measured in peripheral lymphocytes. This effect can be blocked by infusion of alpha-MSH into brain, an attribute that was used to indicate that the effects of LPS infusion occurred by stimulation of endogenous IL-1 and not some other influence of LPS. That suppression of cellular immune responses indeed describes the consequences of elevating IL-1 in brain was shown by determining the time course of effects and thereby demonstrating that rebound enhancement of cellular immune responses did not occur after either IL-1 or LPS. Studies that examined the mechanisms by which brain IL-1 affects immune responses indicated that IL-1 influences peripheral lymphocytes by stimulation of CRF in the central nervous system and that CRF in turn causes suppression of cellular immune responses through activation of both the pituitary-adrenal axis and the autonomic nervous system. These findings have also been observed in another laboratory. Moreover, Brown et al. have shown that IL-1 in brain suppresses macrophage function in addition to the suppression of lymphocyte functions described herein. The physiologic significance of IL-1 actions in the brain on immune responses remains to be determined, but the demonstration that this cytokine influences immune processes by acting in brain opens for study another means by which brain and immune system interact.
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PMID:Widespread activation and consequences of interleukin-1 in the brain. 782 22

Brown Norway (BN) and Sprague Dawley (SD) rats are known to differ in their susceptibility to infection with sporozoites of Plasmodium berghei, as measured by the density of liver schizonts. Because of the known inhibitory effect of non-specific immunomodulators on schizont development, we compared some aspects of the acute phase response in these two rat strains. LPS induced IL-6 production was measured in supernatants of spleen cells and peritoneal macrophages of both strains. SD rats, which are the least susceptible to P. berghei sporozoites, showed significantly higher IL-6 production by macrophages from both sources. When LPS was administered in vivo, SD rats also had a significantly higher IL-6 response. Hepatocytes from both strains were cultured in the presence of IL-6. After three days of culture, alpha 2-Macroglobulin concentrations in the supernatants of SD hepatocytes were much higher than those from BN rats. Kupffer cell depletion in both BN and SD rats was correlated with a significant increase in liver schizont density, but did not abrogate the difference in susceptibility. From these results we conclude that the higher cytokine production capacity of SD rats compared to BN rats, may contribute to the difference in susceptibility to P. berghei sporozoites between these strains, but that other yet unknown factors are also involved.
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PMID:Susceptibility to Plasmodium berghei infection in rats is modulated by the acute phase response. 855 12

Mast cells have been traditionally associated with an acute allergic response. However, their role in regulating chronic inflammatory processes must also be considered in view of evidence that mast cells synthesize and release a number of cytokines. In this study, we have examined the effect of cholera toxin (CT) on peritoneal mast cell IL-6 and TNF-alpha production. Highly purified, freshly isolated, rat peritoneal mast cells from Brown Norway rats were cultured in the presence of CT or its B subunit (CTB) alone or in combination with anti-IgE or bacterial LPS. Histamine release was measured after 10 min; IL-16 and TNF-alpha production was assessed in supernatants after 18 h. We found that CT or CTB alone did not affect histamine release; however, mast cell IL-6 production was significantly enhanced by CT but not by CTB. In contrast, constitutive production of TNF-alpha was inhibited by CT. The effects of CT were similar to our previous observations of the actions of prostaglandin E2 on mast cells. We also examined the effects of CT in combination with other mast cell activating agents. CT had no significant effect on anti-IgE-induced histamine release. An additive effect on IL-6 production was observed in the context of LPS. Forskolin, an agent known to increase intracellular cAMP levels, also induced a significant increase in IL-6 production, whereas TNF-alpha production was decreased. These data have important implications for our understanding of the regulation of mast cell cytokine production and the effects of CT on local cytokine production.
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PMID:Cholera toxin increases IL-6 synthesis and decreases TNF-alpha production by rat peritoneal mast cells. 859 79

Mast cells have been reported to secrete a wide range of immunoregulatory cytokines following IgE-mediated activation and to play an important role in allergic inflammation. We have previously demonstrated that mast cells can also produce certain cytokines following activation with bacterial LPS or prostanoids without preformed mediator release. IL-12 is a potent inducer of IFN-gamma production by T cells and NK cells, and is thought to play a critical role in determining the nature of the local immune response to infection. We here report that highly purified peritoneal mast cells from Brown Norway rats will produce IFN-gamma in response to IL-12 without significant histamine release. IFN-gamma protein was detected by ELISA in supernatants of mast cells cultured with 2 U/ml recombinant mouse IL-12 for between 6 and 24 h. The production of IFN-gamma was dependent on the dose of IL-12 and was significantly inhibited by concurrent treatment with IL-10 or PGE2. Supernatants from IL-12-stimulated mast cells induced MHC class II expression on the mouse epithelial cell line, MODE-K, by an IFN-gamma-dependent mechanism. Peritoneal mast cells cultured following activation with anti-IgE or LPS, under conditions that will induce the production of IL-6, demonstrated no detectable protein production of IFN-gamma. We conclude that mast cells are capable of contributing to the IFN-gamma response to IL-12, but substantial mast cell IFN-gamma production does not occur as a result of IgE-mediated activation. These observations have important implications for the role of the mast cell in local immune regulation.
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PMID:Rat peritoneal mast cells produce IFN-gamma following IL-12 treatment but not in response to IgE-mediated activation. 875 36

Involvement of PAF and kinin in the endotoxin (LPS)-induced hypotension was examined in the rat strains, Brown Norway (B/N);Kitasato (Normal) and B/N-Kitasato rats, intravenous injection of 10 mg/kg LPS caused a hypotension composed on two phases (15 min and 70 min after LPS injection). However in the kininogen-deficient B/N-Katholiek rats. LPS induced only the second phase. Pretreatment with bradykinin (BK) antagonist. Hoe 140 suppressed LPS-induced hypotension of normal rats to the level of Katholiek rats. TCV 309, a PAF-antagonist, suppressed the LPS-hypotension almost completely in the both strains. The reason why the PAF-antagonist showed almost complete inhibition, could be explained by a synergism. Because concomitant injection of a small amount of BK with PAF caused potentiation of the effect of the PAF action. These results suggest that formation of endogenous BK contributes mainly to the 1st phase of LPS-hypotension, and PAF contributes to both phases, by either direct and synergistic actions.
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PMID:Role of synergistic action of PAF and kinin in bacterial endotoxin-induced hypotension in rats. 913 Nov 54


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