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)

The influx of monocytes and neutrophils into the inflamed tissue could be an important aspect in the pathogenesis of inflammatory bowel disease (IBD). A membrane protein involved in the monocyte/neutrophil adherence to endothelium is CD11b/CD18 or alpha M beta 2 (complement receptor type 3 = CR3). In the present study the role of CD11b/CD18 in experimental IBD was studied by treatment with ED7 and OX42, two MoAbs against CD11b/CD18. Colitis was induced in rats by a single, rectal administration of 30 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol 30%. Two hours before and 3 days after induction of colitis, the animals were given an i.v. dose of 0.5 mg of either ED7 or OX42 in 1 ml PBS. Controls received PBS or an irrelevant MoAb. Four days after the last treatment with the antibodies, the rats were killed, and macroscopic damage scores of the colon were determined. Macrophages and granulocytes were studied by immunohistochemistry and quantified by Interaktives Bild Analysen System (IBAS), and myeloperoxidase (MPO) activity in colonic tissue was measured. After treatment with ED7 and OX42 the mean damage score of the colon was reduced from 4.2 in IBD animals to 1.0 and 1.3, respectively. Smaller areas of ulcerations and a decrease in the number of ulcerations were observed compared with PBS-treated rats. Furthermore, the amount of infiltrating monocytes and leucocytes in the submucosa was enormously reduced, as well as MPO activity in the colonic tissue. These results show that treatment with MoAbs against CD11b/CD18 reduces clinical signs of experimental IBD in rats by a partial blockade of infiltrating macrophages and granulocytes.
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PMID:Anti-CD11b/CD18 antibodies reduce inflammation in acute colitis in rats. 764 20

Chicken heterophils activated in vivo following the intraperitoneal (i.p.) administration of Salmonella enteritidis-immune T lymphokines (SE-ILK) have been implicated in the protection against SE organ invasion. SE-ILK induces a heterophilia and directly (or indirectly) activates the granulocytes. The invasion of SE provides the secondary signal for directing activated heterophils to the site of bacterial invasion. We examined the mechanism of adherence within the avian heterophil system using an in vitro bovine serum albumin (BSA) matrix in which neutrophil adherence is primarily CD11/CD18 integrin mediated in mammalian systems. Activated heterophils displayed a four-fold increase in receptor-mediated adherence in vitro to BSA-coated slides as compared to control heterophils from PBS-injected birds. The increased adherence of activated heterophils can be partially blocked by either anti-alpha M (CD11b) or anti-beta 2 (CD18) antibodies in a dose dependent manner. Anti-alpha 3 (CD49c) antibody partially blocked adherence of both normal and activated cells. Fluorescence-activated cell scanning (FACS) analysis of the heterophils shows that both control and SE-ILK-activated heterophils collected at 4 h post injection with SE-ILK or PBS display similar amounts of integrin alpha 3 on their surface. This integrin is constitutively expressed and is responsible for the in vitro adherence of both groups. However, antibodies to the Mac-1 complex (CD11b/CD18) block only the adherence of SE-ILK-stimulated heterophils. Thus, the CD11b/CD18 heterodimer is apparently up regulated in response to the injected SE-ILK and plays a major role in the adherence of activated heterophils. Our studies in chickens parallel human and mouse studies showing the importance of the beta 2 integrins in adherence of activated cells.
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PMID:Differential expression of adhesion molecules by chicken heterophils activated in vivo with Salmonella enteritidis-immune lymphokines. 961 71

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

The success of immunoisolation devices for islet transplantation depends on the properties and biocompatibility of semipermeable immunobarrier membranes. In the present study, we have evaluated the in vitro biocompatibility of the cellulose membrane Spectra/Por 2 (MW no larger than 12- 14,000) for its possible application in islet immunoisolation. The membrane was found to be hydrophilic (octane contact angle: 153.2+/-0.66 degrees) and exhibited decreased protein adsorption. It showed mechanical stability after 1 month of storage in PBS (pH 7.4) with tensile strength, percent elongation, and Young's modulus of 88.88 MPa, 36.22, and 291.8 MPa, respectively. It allowed regulated transport of glucose and insulin in an in vitro diffusion assay. The high viability of NIH3T3 fibroblasts and the inability of lymphocytes to proliferate in vitro on exposure to the membrane leach-out products suggested its noncytotoxic and nonimmunogenic nature. Macrophages, when cultured on membranes, did not show increased expression of inflammatory surface marker such as CD11b/CD18, CD45, CD14, and B 7.2. Image analysis studies showed integrity and intact morphology of mouse islets cultured on and inside the membranes with high viability (91%, 89.7%). These islets also retained their functionality, as judged by insulin secretion. The present study provides sufficient documentation to consider cellulose molecular dialysis membrane Spectra/Por 2 (MW no larger than 12-14,000) as a potential candidate for immunoisolation of islets.
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PMID:Suitability of cellulose molecular dialysis membrane for bioartificial pancreas: in vitro biocompatibility studies. 1118 52

Monocyte chemoattractant protein-1 (MCP-1) stimulates the formation of a collateral circulation on arterial occlusion. The present study served to determine whether these proarteriogenic properties of MCP-1 are preserved in hyperlipidemic apolipoprotein E-deficient (apoE-/-) mice and whether it affects the systemic development of atherosclerosis. A total of 78 apoE-/- mice were treated with local infusion of low-dose MCP-1 (1 microg/kg per week), high-dose MCP-1 (10 microg/kg per week), or PBS as a control after unilateral ligation of the femoral artery. Collateral hindlimb flow, measured with fluorescent microspheres, significantly increased on a 1-week high-dose MCP-1 treatment (PBS 22.6+/-7.2%, MCP-1 31.3+/-10.3%; P<0.05). These effects were still present 2 months after the treatment (PBS 44.3+/-4.6%, MCP-1 56.5+/-10.4%; P<0.001). The increase in collateral flow was accompanied by an increase in the number of perivascular monocytes/macrophages on MCP-1 treatment. However, systemic CD11b expression by monocytes also increased, as did monocyte adhesion at the aortic endothelium and neointimal formation (intima/media ratio, 0.097+/-0.011 [PBS] versus 0.257+/-0.022 [MCP-1]; P<0.0001). Moreover, Sudan IV staining revealed an increase in aortic atherosclerotic plaque surface (24.3+/-5.2% [PBS] versus 38.2+/-9.5% [MCP-1]; P<0.01). Finally, a significant decrease in the percentage of smooth muscle cells was found in plaques (15.0+/-5.2% [PBS] versus 5.8+/-2.3% [MCP-1]; P<0.001). In conclusion, local infusion of MCP-1 significantly increases collateral flow on femoral artery ligation in apoE-/- mice up to 2 months after the treatment. However, the local treatment did not preclude systemic effects on atherogenesis, leading to increased atherosclerotic plaque formation and changes in cellular content of plaques.
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PMID:Local monocyte chemoattractant protein-1 therapy increases collateral artery formation in apolipoprotein E-deficient mice but induces systemic monocytic CD11b expression, neointimal formation, and plaque progression. 1257 50

Altered IL-6 production regulation is associated with the pathogenesis of chronic inflammatory diseases, lymphoid malignancies, chronic infectious processes and certain types of autoimmune conditions. Here, we examine the effects of pollutants on IL-6 levels in mice serum and in culture supernatants of spleen cells. Mice were treated with vehicles (PBS or olive oil), benzo[alpha]pyrene (B[alpha]P, 100 mg/kg body weight), 2-bromopropane (2-BP, 3.5 g/kg), phenol (21.2 mg/kg), or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 15 mg/kg). Serum IL-6 levels were significantly increased in the TCDD-treated group at 24 hours and 48 hours after a single exposure, whereas exposure to phenol, B[alpha]P or 2-BP did not cause a significant difference. IL-6 levels in culture supernatants of splenocytes were not affected at 24 hours and 48 hours after a single pollutant treatment. A repeated dose of TCDD (once/week for 4 weeks) resulted in a significant elevation of IL-6 levels in serum and its spontaneous production in culture supernatants of splenocytes. Repeatedly TCDD-treated mice contained more CD11b (Mac-1)-positive cells in the spleen and higher titers of tissue-specific autoantibodies than the vehicle-treated group. These results suggest that repeated exposure to TCDD might impair the regulation of immune response by deregulating the production of IL-6.
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PMID:Effects of benzo[alpha]pyrene, 2-bromopropane, phenol and 2,3,7,8-tetrachlorodibenzo-p-dioxin on IL-6 production in mice after single or repeated exposure. 1292 79

Flt3 ligand (Flt3-L) is a growth factor for dendritic cells and induces type 1 T cell responses. We recently reported that Flt3-L prevented OVA-induced allergic airway inflammation and suppressed late allergic response and airway hyper-responsiveness (AHR). In the present study we examined whether Flt3-L reversed allergic airway inflammation in an established model of asthma. BALB/c mice were sensitized and challenged with OVA, and AHR to methacholine was established. Then mice with AHR were randomized and treated with PBS or 6 microg of Flt3-L i.p. for 10 days. Pulmonary functions and AHR to methacholine were examined after rechallenge with OVA. Treatment with Flt3-L of presensitized mice significantly suppressed (p < 0.001) the late allergic response, AHR, bronchoalveolar lavage fluid total cellularity, absolute eosinophil counts, and inflammation in the lung tissue. There was a significant decrease in proinflammatory cytokines (TNF-alpha, IL-4, and IL-5) in bronchoalveolar lavage fluid, with a significant increase in serum IL-12 and a decrease in serum IL-5 levels. There was no significant effect of Flt3-L treatment on serum IL-4 and serum total IgE levels. Sensitization with OVA significantly increased CD11b(+)CD11c(+) cells in the lung, and this phenomenon was not significantly affected by Flt3-L treatment. These data suggest that Flt3-L can reverse allergic airway inflammation and associated changes in pulmonary functions in murine asthma model.
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PMID:Flt-3 ligand reverses late allergic response and airway hyper-responsiveness in a mouse model of allergic inflammation. 1506 83

Bone marrow-derived endothelial progenitor cells (EPCs) have the ability to migrate to ischemic organs. However, the signals that mediate trafficking and recruitment of these cells are not well understood. Using a functional genomics strategy, we determined the genes that were upregulated in the ischemic myocardium and might be involved in EPC recruitment. Among them, CD18 and its ligand ICAM-1 are particularly intriguing because CD18 and its heterodimer binding chains CD11a and CD11b were correspondingly expressed in ex vivo-expanded EPCs isolated from rat and murine bone marrows. To further verify the functional role of CD18 in mediating EPC recruitment and repair to the infarcted myocardium, we used neutralizing antibody to block CD18. Blockade of CD18 in EPCs significantly inhibited their attachment capacity in vitro and reduced their recruitment to the ischemic myocardium in vivo by 95%. Moreover, mice receiving EPCs that were treated with control isotype IgG exhibited significantly increased capillary density in the infarct border zone, reduced cardiac dilatation, ventricular wall thinning, and fibrosis when compared with myocardial infarction mice receiving PBS and CD18 blockade reversed the EPC-mediated improvements to the infarcted heart. Thus, our results suggest an essential role of CD18 in mediating EPC recruitment and the subsequent functional effects on the infarcted heart.
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PMID:Essential role of ICAM-1/CD18 in mediating EPC recruitment, angiogenesis, and repair to the infarcted myocardium. 1682 78

It has not been resolved whether macrophages or airway epithelial cells primarily respond to infectious and inflammatory stimuli and initiate a cell-to-cell inflammatory interaction within the airways. We hypothesized that the airway epithelial cells are primary responders that activate macrophages in response to environmental stimuli. To investigate the unilateral contribution of airway epithelial cells in the activation of macrophages, we developed an in vitro system in which the primary mouse tracheal epithelial cells (MTEC) and primary bone marrow-derived macrophages (BMDM) were incubated together for a brief period of time in a Transwell culture plate. MTEC were transfected with adenoviral vectors that express a constitutively active form of IKK2 (Ad-cIKK2), Ad-beta-Gal, or PBS for 48 h before incubating with the macrophages. Macrophage activation was determined by measuring surface expression of CD11b, activation of NF-kappaB, phagocytic activity and production of reactive oxygen species, and cyclooxygenase (COX)-2 gene expression and production of prostaglandins. Macrophage adherence to epithelial layer was confirmed by CD68 immunostaining and scanning electron microscopy. MTEC cells transfected with Ad-cIKK2 produced increased amounts of IL-6, mouse GRO-alpha, TNF-alpha, and prostaglandin (PG)E2. Exposure of BMDM to MTEC, transfected with Ad-cIKK2, led to an increase in the CD11b expression and increased adherence of macrophages to the epithelial cell layer. NF-kappaB activation, COX-2 gene expression, and PGD2 synthesis were also increased in BMDM that were incubated with MTEC transfected with Ad-cIKK2. These data suggest that airway epithelial cells potentially play a primary role in generating inflammatory signals that result in activation of macrophages.
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PMID:Inhibitory kappaB kinase 2 activates airway epithelial cells to stimulate bone marrow macrophages. 1720 85

A mouse model for allergic airway inflammation involving ovalbumin (OVA) sensitization and challenge has been developed that reproduces hallmark features of human asthma and has provided valuable insight into the mechanisms by which this disease occurs. Cellular infiltrate in lungs of mice used in this model have conventionally been evaluated using histological examination of tissue sections and light microscopic analysis of lung lavage samples. As an alternative or complementary approach for characterizing cellular infiltrate, we developed a multicolor fluorescence-activated cell sorter (FACS) method involving the simultaneous detection of seven different markers on lung cell suspensions: CD4, CD8, B220, CD11b, Gr-1, CD49b, and FcepsilonRI. Only some of these cell types increased in OVA-challenged mice compared to PBS controls, including the CD4(+), B220(+), CD11b(+), and FcepsilonRI(+) groups. We also examined subpopulations of cells for coexpression of these markers and dissected heterogeneous populations as further evaluation procedures to characterize the cellular infiltrate resulting from OVA challenge. Finally, we combined FACS with real-time PCR to analyze certain cell types in terms of mRNA levels for factors involved in asthma, including GATA-3 and IL-1beta. Overall, these FACS-based techniques provide a powerful approach for analyzing cellular profiles in lung tissue from mice used in the mouse model of asthma and may also prove valuable in evaluating cellular infiltrates for other models of inflammation and immune responses.
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PMID:A new approach for analyzing cellular infiltration during allergic airway inflammation. 1782 15


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