Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The leukocyte adhesion glycoprotein complex CD11/CD18 has been shown to be important in mediating neutrophil accumulation at sites of inflammation in many experimental models. The exception is the lung, where neutrophil accumulation into the airspaces can be CD18-dependent and -independent, according to the stimulus used to induce pulmonary inflammation. By using the anti-CD18 mAb 60.3, this study examined the role of CD18 on neutrophil accumulation in the lungs of rabbits induced by a local intrabronchial instillation of C5a or interleukin-1 alpha (IL-1 alpha) into the upper lung lobes. For comparison, cutaneous inflammation was induced in the same animals by intradermal injection of the same mediators. Pretreating rabbits with 60.3 abolished accumulation of 111In-labeled neutrophils in skin induced by both C5a and IL-1 alpha. In contrast, in the same animals, C5a-induced accumulation of neutrophils in the lung was not significantly affected by 60.3, while neutrophil accumulation in response to IL-1 alpha showed a significant, but not absolute, dependency on CD18. External gamma scintigraphy of 111In-labeled neutrophils demonstrated that the kinetics of cell retention in the lung was similar for both C5a and IL-1 alpha. In summary, accumulation of neutrophils to sites of inflammation in cutaneous inflammation shows an absolute dependency on CD18, while migration of these cells to sites of inflammation in the lung can be largely independent of this adhesion molecule. These data indicate that the mechanisms responsible for accumulation of neutrophils in cutaneous and pulmonary inflammation are different.
Am J Respir Cell Mol Biol 1994 Apr
PMID:Disparate role of the beta 2-integrin CD18 in the local accumulation of neutrophils in pulmonary and cutaneous inflammation in the rabbit. 751 Sep 85

Transcription of the gene encoding the endothelial cell-leukocyte adhesion molecule (ELAM-1; E-selectin) is induced in response to various cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1. A DNase I-hypersensitive site in the 5' proximal promoter region of the E-selectin gene is observed in human umbilical vein endothelial cells only following TNF-alpha treatment, suggesting the presence of a TNF-alpha-inducible element close to the transcriptional start site. Transient transfection studies in endothelial cells demonstrated that 170 bp of upstream sequences is sufficient to confer TNF-alpha inducibility. Systematic site-directed mutagenesis of this region revealed two regulatory elements (-129 to -110 and -99 to -80) that are essential for maximal promoter activity following cytokine treatment. Protein binding studies with crude nuclear extracts and recombinant proteins revealed that the two elements correspond to three NF-kappa B binding sites (site 1, -126; site 2, 116; and site 3, -94). All three sites can be bound by NF-kappa B when used as independent oligonucleotides in mobility shift assays. However, within the context of a larger promoter fragment, sites 2 and 3 are preferentially occupied over site 1. These data are consistent with results obtained in transfection studies demonstrating that mutations in sites 2 and 3 are more detrimental than mutations within site 1. Hence, inducibility of the E-selectin gene requires the interaction of NF-kappa B proteins bound to multiple regulatory elements.
Mol Cell Biol 1994 Sep
PMID:Three NF-kappa B binding sites in the human E-selectin gene required for maximal tumor necrosis factor alpha-induced expression. 752 May 26

Previous studies have demonstrated that alveolar macrophages (AMphis) adherent to plastic release interleukin-8 in response to lipopolysaccharide (LPS). We sought to determine whether LPS could also alter surface adhesion molecule expression and thus modulate additional AMphi adhesive interactions. Canine AMphis obtained by bronchoalveolar lavage of excised lung were adhered onto tissue culture plastic and exposed to LPS (0.01 to 100 ng/ml). Expression of beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) was subsequently determined by flow cytometry, a cDNA probe to canine ICAM-1 was used to quantify ICAM-1 mRNA, and changes in adhesion molecule function were assessed by evaluating the extent of homotypic aggregation. ICAM-1 and CD11a/CD18 were present on freshly isolated AMphis. CD11b/CD18 and CD11c/CD18 were expressed at lower levels. Nonadherent AMphis expressed a pattern of beta 2 integrin and ICAM-1 comparable to adherent cells. During short-term LPS stimulation (3 h), adherent AMphis increased both the synthesis and expression of ICAM-1. CD18 expression was either decreased or remained unchanged with LPS stimulation. LPS stimulation in vitro (> 0.01 ng/ml) enhanced the homotypic aggregation of adherent AMphis. Aggregation was blocked by monoclonal antibodies to ICAM-1 (CL18/6) and CD11a (R7.1) and CD18 (R15.7). Similar kinetics were found for expression of ICAM-1 and homotypic aggregation, suggesting that up-regulation of ICAM-1 is a major determinant of the LPS-stimulated aggregation of AMphis.
Am J Respir Cell Mol Biol 1994 Sep
PMID:Induction of intercellular adhesion molecule-1 by lipopolysaccharide in canine alveolar macrophages. 752 15

Protectin (CD59) is a complement regulatory protein which blocks the membrane attack complex during complement activation. CD59 was identified on the human sperm surface by means of H19, an IgG1 anti-protectin mouse monoclonal antibody. Using indirect immunofluorescence, flow cytometry and immunoperoxidase, CD59 was found to be present on the whole plasma membrane including the head and tail of fresh ejaculated, capacitated and acrosome-reacted spermatozoa. Immunoperoxidase staining of normal testicular sections indicated that this protein was already present on intraluminal germ cells. Analysis of this sperm protein by gel electrophoresis and immunoblotting revealed that its molecular weight of 20 kDa was comparable to that of CD59 expressed on peripheral blood cells (erythrocytes, lymphocytes) and that it was bound to the membrane through a glycophospholipid tail which could be released after treatment with phosphatidylinositol-specific phospholipase C. Associated to membrane cofactor protein (CD46) and decay accelerating factor (CD55) located in the acrosomal membranes, CD59 may participate to the protection of male gametes against complement-mediated damage as they travel through the female genital tract. Moreover CD59, known as an adhesion molecule involved in lymphocyte rosettes, may also participate in cell to cell adhesion during gametic interaction since H19 inhibited sperm binding and reduced the penetration rate and index during the hamster egg penetration test.
Mol Reprod Dev 1994 Jul
PMID:Expression of the complement regulatory protein CD59 on human spermatozoa: characterization and role in gametic interaction. 752 80

We examined whether antirheumatic drugs alter cytokine- or lipopolysaccharide-induced expression of adhesion molecules on vascular endothelial cells. Human umbilical cord vein endothelial cells were co-cultured with various antirheumatic drugs in the presence of inflammatory cytokines, and adhesion molecule expression was measured by cell enzyme-linked immunosorbent assay and Northern blot analysis. Among these antirheumatic drugs, gold sodium thiomalate significantly inhibited intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on vascular endothelial cells and suppressed cellular binding between human monocytic cell lines, including U937 and HL-60 cells, and interleukin-1 beta-stimulated vascular endothelial cells. It is speculated that down-regulation of adhesion molecules might be one of the novel mechanisms of action of gold sodium thiomalate.
Mol Pharmacol 1994 Oct
PMID:Gold sodium thiomalate down-regulates intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on vascular endothelial cells. 752 48

Neutrophil (PMN) sequestration in the pulmonary microvasculature precedes the migration of these cells into the airspaces in inflamed lungs. Intratracheal instillation of the heat-killed organism Corynebacterium parvum in the rat induces an alveolitis in which PMN constitute 70 to 80% of the total cell count in the bronchoalveolar lavage (BAL). This acute alveolitis results in increased sequestration in the pulmonary microvasculature of 51Cr-labeled PMN when compared with control lungs. The aims of this study were to confirm this increased pulmonary PMN sequestration using unlabeled cells and to assess the function and adhesion molecule expression of such sequestered PMN. We counted the number of PMN and erythrocytes obtained by pulmonary vascular lavage (PVL) and compared the ratio of these two cell types in PVL and peripheral blood (PB) as a measure of the sequestration of PMN in the pulmonary vasculature. Compared with control animals, PVL in C. parvum-treated rats had higher PMN counts, which could not be accounted for by the PB leukocytosis. Sequestration of PMN in the pulmonary microvasculature depends on several factors, including the upregulation of adhesion molecules on both PMN and endothelial surfaces and the ability of the cells to deform when passing through the microcirculation. Cells obtained from the PVL were less deformable than PB cells in control but not in C. parvum-treated animals. The expression of the CD18 integrin on PMN obtained from the PVL of C. parvum-treated animals was increased compared with cells from control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Nov
PMID:Deformability and CD11/CD18 expression of sequestered neutrophils in normal and inflamed lungs. 757 88

We have previously reported that the mutations of the myelin P0 gene were completely linked with Charcot-Marie-Tooth neuropathy type 1B (CMT1B) in two families. In this study we found a different mutation in another family with CMT1B. The mutation, a methionine substitution for isoleucine at amino acid position 30, is located in the extracellular domain, which constitutes an immunoglobulin domain responsible for the function of P0 as an adhesion molecule. The results confirmed that P0 is a gene responsible for CMT1B.
Hum Mol Genet 1993 Sep
PMID:Mutation of the myelin P0 gene in Charcot-Marie-Tooth neuropathy type 1B. 769 26

In an effort to identify aberrantly expressed genes in v-rel-induced tumors, monoclonal antibodies were developed that reacted selectively with avian B-cell tumors. One antibody, HY78, immunoprecipitated a 120-kDa glycoprotein (p120) from cells that express v-rel. N-terminal amino acid sequencing of p120 identified a 27-amino-acid sequence that is also present in DM-GRASP, an adhesion molecule belonging to the immunoglobulin superfamily. Evidence from tissue distribution, immunological cross-reaction, PCR amplification, cDNA cloning, and DNA sequence shows that p120 is indeed DM-GRASP. Northern (RNA) analysis using a probe from the DM-GRASP gene identified a 5.3-kb transcript in mRNA from bursa, thymus, and brain as well as from v-rel-induced B-cell lymphomas but not from bursal B cells. The induction of this protein by v-rel during the development of bursal B-cell lymphomas appears, therefore, to be ectopic in nature. Overexpression of v-rel or c-rel in chicken embryonic fibroblasts, B-cell lines, and spleen mononuclear cells induces the expression of DM-GRASP. The ratio of DM-GRASP to v-Rel was fivefold higher than that of DM-GRASP/c-Rel in a B-cell line, DT95. Interestingly, the presence of HY78 antibody inhibits the in vitro proliferation of v-rel-transformed cells but not cells that immortalized by myc. These data suggest that DM-GRASP is one of the genes induced during v-rel-mediated tumor development and that DM-GRASP may be involved in the growth of v-rel tumor cells.
Mol Cell Biol 1995 Mar
PMID:v-rel Induces ectopic expression of an adhesion molecule, DM-GRASP, during B-lymphoma development. 786 70

We have recently shown that interferon-gamma (IFN-gamma) stimulated immunocytochemical staining of the intercellular adhesion molecule ICAM-1 may be dependent on inositol phosphate formation in the human renal carcinoma cell line CaKi-1. In the present study we investigated the possible role of GTP-binding proteins (G-proteins) during IFN-gamma signalling. Preincubation of CaKi-1 cells for 24 h with increasing amounts of pertussis toxin (PT) or cholera toxin (CT), two regulators of G-protein activity, inhibited IFN-gamma induced ICAM-1 staining. Preincubation with PT or CT for 24 h also inhibited IFN-gamma induced inositol 1-monophosphate (Ins 1-P), inositol 1,4 bisphosphate (Ins 1,4-P2) and inositol 1,4,5 trisphosphate (Ins 1,4,5-P3) formation. Our findings suggest that IFN-gamma induced ICAM-1 staining and inositol phosphate formation in CaKi-1 cells is dependent on a PT and CT sensitive signalling pathway. This may reflect a role for G-proteins in the coupling of IFN-gamma receptor activation and phospholipase C catalyzed phosphoinositide hydrolysis.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Effects of pertussis and cholera toxin on the interferon-gamma stimulated immunocytochemical staining of ICAM-1 and inositol phosphate formation in a human renal carcinoma cell line. 790 88

Local regulation of immune and inflammatory responses within the alveolar space is a critical aspect of normal pulmonary host defense. The type I and type II epithelial cells that line the alveolar space are in intimate contact with lymphocytes and macrophages within the alveolar space and are ideally situated to provide regulatory signals to these effector cells. The present studies were undertaken to investigate the expression by rat alveolar epithelial cells in vitro and in vivo of intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule that is involved in migration and activation of T cells and macrophages. An antibody specifically blocking rat ICAM-1 (mAb 1A29) inhibited the adherence of activated T lymphoblasts to monolayers of type II alveolar epithelial cells. The expression of ICAM-1 protein by alveolar epithelial cells in vitro was confirmed both by immunofluorescence microscopy and by Western blot analysis. However, in each instance, ICAM-1 was not detected in type II cells the day of isolation, but appeared at low levels after 1 day and in abundance throughout the monolayer after 2 days, with sustained expression thereafter. This suggested that ICAM-1 expression might be a type I cell feature, which was induced as isolated type II cells underwent transformation towards the type I cell-like phenotype in vitro. Using immunofluorescence microscopy on frozen sections of normal lung, ICAM-1 was found in a linear distribution along the alveolar space, consistent with expression on type I cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Jan
PMID:Differentiation-related expression of ICAM-1 by rat alveolar epithelial cells. 809 43


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