Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating immune complexes are considered to have a profound effect on host defense mechanisms against invading pathogens and to modulate cellular interactions required for an appropriate course of the immune response. In this study we have investigated the influence of polymeric IgG (used as a model system for immune complexes) on accessory functions of human monocytes. We show that a short (1 hr) incubation of human monocytes in the presence of polymeric IgG (16 hr prior to antigen pulsing) led to a significant decrease of these cells' antigen-presenting capacity while accessory functions in alloantigen- or mitogen-driven proliferation systems remained unimpaired. The polymeric IgG-induced impairment of antigen presentation, which was assessed by diminished proliferation of antigen-reactive T cells following stimulation by antigen-pulsed polymeric IgG-treated or Dulbecco's phosphate-buffered saline (PBS-D)-treated control monocytes, could not be attributed to the generation of suppressor mechanisms (no release of soluble suppressor factors, no induction of suppressive monocytes). The release of interleukin-1 by polymeric IgG-treated monocytes and PBS-D-treated monocytes was comparable and polymeric IgG did not down modulate major histocompatibility complex (MHC) class II molecules already expressed in the monocyte plasma membrane. Profound changes in the monocyte plasma membrane occurring subsequent to polymeric IgG treatment possibly accompanied by altered kinetics of MHC class II reexpression are likely to contribute to the observed decrease of antigen presentation.
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PMID:Effect of polymeric IgG on human accessory cell function. 293 62

To explore the mechanisms responsible for the development of tolerance to allografts after intrathymic (IT) injection of alloantigen, the well-defined model of experimental autoimmune encephalomyelitis (EAE), which mimics the human autoimmune disease multiple sclerosis, was used. This inflammatory neurologic syndrome is initiated by myelin basic protein (MBP)-reactive CD4+ T lymphocytes restricted to self-MHC class II molecules. Naive adult, EAE-susceptible Lewis (RT1(1) rats were treated IT, i.v., or i.p. with a single dose (100 micrograms) of guinea pig-myelin basic protein (GP-MBP 1-176) in PBS plus 1 ml rabbit anti-rat lymphocyte serum i.p. Twenty-one days later, all rats were challenged by intradermal hind footpad injections of 50 micrograms GP-MBP in PBS emulsified in CFA. Only IT, but not i.p. or i.v., administration of GP-MBP plus anti-lymphocyte serum conferred marked resistance to a subsequent systemic challenge of GP-MBP, as demonstrated by the prevention of weight loss and paralysis characteristic of EAE. The IT administration dramatically decreased the size and number of histologic perivascular infiltrates observed per visual field in spinal cord of the tolerant animals and decreased GP-MBP-specific T lymphocyte in vitro proliferation (p < 0.01), whereas proliferation to a nonspecific mitogen (Con A) was not altered. With the addition of rIL-2, the decreased Ag-specific proliferative responses of IT-treated animals increased to control levels. Adoptive transfer of 100 x 10(6) splenocytes from tolerant hosts i.v. to naive syngeneic Lewis rats challenge with 100 micrograms GP-MBP in CFA had no effect on clinical or histologic EAE. Exposure of MBP to maturing thymocytes results in functionally immunounresponsive lymphocytes and prevention of autoimmune EAE.
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PMID:Immunological tolerance to a defined myelin basic protein antigen administered intrathymically. 752 8

Langerhans cells (LC) are Ag-presenting cells required for induction of primary immune responses in skin. After activation by Ag, LC express increased levels of MHC class II Ag, exhibit increased accessory cell activity, and migrate to regional lymph nodes where they stimulate T cells. One of the earliest manifestations of LC activation is the accumulation of increased amounts of IL-1 beta mRNA in LC within 15 min after exposure to contact allergens in vivo. To determine if enhanced IL-1 beta production by LC could be causally linked to epicutaneous sensitization, we injected IL-1 beta intradermally into the ears of BALB/c mice and extracted total epidermal RNA 4 h later. A quantitative reverse transcriptase-polymerase chain reaction technique was used to compare changes in IL-1 alpha, IL-1 beta, macrophage inflammatory protein 2, IL-10, TNF-alpha, and 1-A alpha chain mRNA signals caused by intradermally-injected IL-1 beta to those caused by intradermal IL-1 alpha or TNF alpha, or by topical application of the contact allergen trinitrochlorobenzene (3% TNCB). Intradermal injection of 25 ng IL-1 beta resulted in 5-to 100-fold enhancement of mRNA signals for IL-1 alpha, IL-1 beta, MIP-2, IL-10, TNF alpha, and class II I-A alpha, mimicking the changes caused by allergen. In contrast, injection of equivalent amounts of IL-1 alpha or TNF alpha did not significantly alter the epidermal cytokine pattern. Simulating the effects of topically applied TNCB, intradermally-injected IL-1 beta (but not IL-1 alpha or TNF alpha) also caused enhancement of LC MHC class II expression. In addition, LC derived from IL-1 beta-injected skin were 2 to 3 times more potent accessory cells in an anti-CD3 proliferation assay than LC from IL-1 alpha or sham-injected skin. Finally, injection of hamster anti-mIL-1 beta mAb into the skin prior to TNCB treatment completely prevented sensitization to this allergen, although injections of similar amounts of hamster anti-mIL-1 alpha mAb or PBS were without effect. Taken together, our data indicate that dendritic cell-derived IL-1 beta may be a critical molecule required for initiation of primary immune responses in skin.
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PMID:An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin. 847 27

The role of endogenous interferon-gamma (IFN gamma) in the development of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone BB rats was evaluated. Several groups of these animals were treated under different, experimental conditions with a purified polyclonal antibody (Ab), antirat IFN gamma. The results show that when administered at doses of 100 or 200 micrograms/week from the 30/33th until the 105th day of age, the anti-IFN gamma Ab reversibly reduced the incidence of IDDM compared to that in control rats treated with either irrelevant rabbit IgG or PBS. Moreover, when given up to the 105th day of age, these doses of anti-IFN gamma Abs exerted comparable preventive effects regardless of whether application started as early as within 24 h after birth or at the end of the prediabetic period (e.g. 70/75 days). In contrast, under none of the above experimental conditions did larger doses of anti-IFN gamma Ab (500 micrograms or 1 mg/week) exert antidiabetogenic effects in the BB rats. Apparently, this was due to the exuberant production of neutralizing Abs elicited by the large amount of the xenogeneic Ab injected. At histoimmunological analyses, the BB rats treated with 200 micrograms/ week anti-IFN gamma Abs from 30-80 days of age exhibited a milder insulitic process along with diminished spleen frequency of activated lymphoid cells (MHC class II and interleukin-2 receptor positive). Taken together, these results provide further in vivo evidence for the central pathogenic role of IFN gamma in BB rat IDDM and anticipate the usefulness of specific IFN gamma inhibitors in the prevention of the disease in the clinical setting. Defining novel and less immunogenic forms of specific IFN gamma inhibitors than xenogeneic Abs is important for improving the efficiency of anti-IFN gamma-oriented approaches.
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PMID:Prevention of spontaneous autoimmune diabetes in diabetes-prone BB rats by prophylactic treatment with antirat interferon-gamma antibody. 897 15

Monocytes and macrophages mediate cytotoxicity after appropriate activation and thus represent effectors secondary to T lymphocytes and natural killer (NK) cells. However, very little is known about the role of activated monocytes in organ allograft rejection. In this study, isogeneic (LEW to LEW) and fully allogeneic (DA to LEW) rat kidneys were grafted to bilaterally nephrectomized recipients. Four days after transplantation a comprehensive sample of leucocytes was recovered by perfusion of the recipients' vasculature with phosphate-buffered saline containing EDTA (PBS/EDTA). Monocytes were enriched by density gradient centrifugation and their physical parameters and immunophenotype were investigated by flow cytometry in comparison with untreated, specified pathogen-free (SPF) LEW rats. Isotransplantation and allotransplantation of kidneys dramatically increased the absolute number of intravascular monocytes in the recipient. Analysis of NKR-P1 (CD161), CD4, CD62L, CD43, CD11a, CD18 and MHC class II expression identified at least two monocyte populations in all experimental groups. In graft recipients it was evident that activated monocytes were able to express and upregulate NKR-P1 and CD8, which have not been detected in these cells to date. If activated monocytes utilize NKR-P1 and CD8, by analogy to NK cells and lymphocytes these cells may be endowed with additional pathways to upregulate cytolytic functions and effect allograft damage.
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PMID:Phenotype of rat monocytes during acute kidney allograft rejection: increased expression of NKR-P1 and reduction of CD43. 960 Mar 14

An improved method of removing rat corneal endothelial sheets for study of endothelial pathology is described. The method was validated by examining morphological changes and changes in expression of major histocompatibility complex (MHC) and intercellular adhesion molecule (ICAM)-1 on endothelium undergoing immunological rejection. PVG strain rats received LEW strain corneal transplants or corneal isografts. Just prior to and during graft rejection, animals were killed, together with a group of untreated animals. The corneal stroma was injected with dispase or PBS, the cornea was carefully removed, fixed in acetone and the endothelium was gently peeled off and flattened on to a glass slide. Morphological changes, together with MHC class I, class II and ICAM-1 expression were visualised by immuno-histochemical staining and quantified by image analysis. Near complete endothelial sheets were obtained by this method. Because of the thin cell layer, there was minimal background staining, permitting rejection-associated changes to be clearly seen. MHC class I expression on normal endothelium was low and not significantly increased on endothelial cells of allografts at the time of rejection compared with controls (P = 0.1). MHC class II and ICAM-1 were induced de novo, expression being significantly higher on allografts than on isografts (P = 0.004 for MHC class II and P = 0.01 for ICAM-1). MHC class I and II and ICAM-1 were expressed on many infiltrating cells. Thus, this preparation method permits clear identification of the distribution and morphology of infiltrating cells and other mediators of the immune response in the entire donor endothelium. It confirms that MHC class I expression is low during rejection, while MHC class II and ICAM-I are induced de novo and strongly expressed.
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PMID:An improved method for examining the corneal endothelium during graft rejection in the rat. 999 Mar 27

To examine the direct effects of IL-4 on peripheral nervous system (PNS) we injected recombinant rat IL-4 (rrIL-4) into the sciatic nerve of normal adult Lewis rats. Histopathological and immunohistochemical observations revealed that 1 day after injection, a large number of macrophages and MHC class II-positive cells appeared within both the perineurium and endoneurium. Only few CD4(+)and CD8(+)T cells existed in the endoneurium. From day 4 to day 7, we observed a gradual decline of inflammation, but the number of infiltrates in rrIL-4 injected nerves was significantly higher compared with sterile PBS-injected control group. On the contrary, demyelination affected significantly fewer nerve fibres in the rrIL-4-injected nerves compared with control group on day 7. Intraneural injection of rrIL-4 results in high grade inflammation and mild demyelination in the PNS.
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PMID:High inflammation and mild demyelination in the peripheral nervous system induced by an intraneural injection of RR interleukin-4. 1084 69

We review our methods for definition and phenotypical characterisation of normal and activated rat monocytes. To obtain a comprehensive sample of all blood monocytes including cells from the marginal pool of the blood stream, we extensively perfuse the extrapulmonary circulation with cold PBS/EDTA. Normal rat monocytes are isolated from untreated specified pathogen-free male LEW rats. In vivo activated monocytes are investigated after three days of infusion of recombinant IFN-gamma or during acute renal allograft rejection. Rat monocytes are defined by reactivity with mAbs ED1 and ED9, detecting a lysosomal membrane antigen and a member of the signal-regulatory protein family, respectively, as well as by expression of CD11b. Concomitantly rat monocytes are characterized by the absence of CD5, the absence of the B cell form of CD45R, and the absence of reactivity with mAb RP-1. The majority of the monocytes from untreated LEW rats are CD4+, CD11a(high), CD18high, CD43high, CD62-L-, CD161-, and MHC class II-. Upon stimulation of the immune system in vivo, a second monocyte population increases in number. These cells have a larger diameter and an increased granularity. They are CD4-, CD11a(int), CD18int, CD43low, CD62-L+, CD161int, and MHC class II+. Although some reagents are not yet available (e.g. antibodies against rat CD14 and CD16), rat monocytes can be defined and their state of activation can be characterized. The functionally important population of monocytes, which have already marginated, is accessible by perfusion and relatively high monocyte numbers are isolated per rat. As specified pathogen-free rats are available and numerous experimental systems involving acute or chronic inflammation have been established in rats, differentially activated monocytes may be investigated. The rat is thus a suitable experimental animal for basic research on monocytes.
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PMID:Monocytes in the rat. 1087 93

NO is involved in the regulation of immune responses. The role of NO in the pathogenesis of experimental allergic encephalomyelitis (EAE) is controversial. In this study, 3-morpholinosydnonimine (SIN-1), an NO donor, was administered to Lewis rats on days 5-7 postimmunization, i.e., during the incipient phase of EAE. SIN-1 reduced clinical signs of EAE compared with those in PBS-treated control rats and was accompanied by reduced ED1(+) macrophages and CD4(+) T cell infiltration within the CNS. Blood mononuclear cells (MNC) obtained on day 14 postimmunization revealed that SIN-1 administration enhanced NO and IFN-gamma production by blood MNC and suppressed Ag- and mitogen-induced proliferative responses. MHC class II, B7-1 and B7-2 were down-regulated in SIN-1-treated EAE rats. Simultaneously, frequencies of apoptotic cells among blood MNC were increased. In vivo, SIN-1 is likely to behave as an NO donor. Administration of SIN-1 induced NO production, but did not affect superoxide and peroxynitrite formation. Enhanced NO production during the priming phase of EAE thus promotes apoptosis, down-regulates disease-promoting immune reactivities, and ameliorates clinical EAE, mainly through SIN-1-derived NO, without depending on NO synthase.
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PMID:SIN-1, a nitric oxide donor, ameliorates experimental allergic encephalomyelitis in Lewis rats in the incipient phase: the importance of the time window. 1131 25

We have studied the effects of treatment with recombinant human (rh)IL-6 on clinical, histological and immunological parameters of protracted relapsing (PR) experimental allergic encephalomyelitis (EAE) in DA rats. rhIL-6 (50 microg/rat subcutaneously/day) was given under three different regimens, as early prophylaxis, from 1 day prior to 14 days after immunization, in late prophylaxis, from day +7 until day 21 post-immunization (p.i.) and therapeutically to rats with clinical signs of EAE from day 14 to day 28 p.i. Although rhIL-6 failed to modulate the course of PR-EAE when administered as the early prophylactic regimen, it exerted clear-cut favourable effects on the course of the disease if was administered either as later prophylactic or as therapeutic treatment. Under these conditions, rhIL-6 accelerated recovery from EAE attacks and reduced/milded subsequent EAE episodes as compared to either PBS- or heat-inactivated rhIL-6-treated control rats. In agreement with this clinical effect, relative to PBS-treated rats, the animals injected with rhIL-6 exhibited lower numbers of MHC class II(+) and CD4(+) cells in their spinal cords. rhIL-6-treatment also profoundly modulated the endogenous cytokine network, the treated rats displaying increased numbers of spleen cells expressing mRNA transcripts of the anti-inflammatory cytokines IL-10 and TGF-beta along with simultaneously reduced numbers of mRNAs for TNF-alpha. In addition, upon ex vivo exposure to either myelin basic protein peptide 63-88 (MBP63-88) or to phytoaemagglutinin A, the numbers of IFN-gamma secreting splenocytes was also significantly reduced (ELISPOT analysis) in rhIL-6-treated rats as compared to PBS-treated controls.
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PMID:Curative effects of recombinant human Interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis. 1143 71


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