UNIPROT:O95477 - FACTA Search

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Query: UNIPROT:O95477 (membrane-bound)
29,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD14 represents the most specific marker for monocytes/macrophages. It has been demonstrated in vitro that monocytes/macrophages lose this antigen upon activation. Results of studies investigating the expression of membrane-bound CD14 on the surface of monocytes/macrophages in sarcoidosis patients are controversial. To investigate whether the soluble form of CD14 reflects monocyte/macrophage activation in sarcoidosis, serum levels of soluble CD14 were determined concurrently with other serum markers of monocyte/macrophage activation (neopterin, angiotensin-converting enzyme) in 50 consecutive patients with bioptically confirmed sarcoidosis. The patients were allocated to three groups according to disease activity and therapy. The soluble interleukin-2 receptor in serum and the CD4/CD8 ratio in lavage fluid were used to monitor T-lymphocyte activation. No significant differences in serum or bronchoalveolar lavage levels of soluble CD14 were observed in patients with active or inactive sarcoidosis. Despite the presence of normal soluble CD14 serum concentrations a correlation with serum neopterin and angiotensin-converting enzyme was found in active sarcoidosis (soluble CD14 versus neopterin, rs = 0.61 and 0.65, P < 0.05 and 0.01, respectively; soluble CD14 versus angiotensin-converting enzyme, rs = 0.6 and 0.72, P < 0.02 and 0.003, respectively). A correlation between soluble CD14 and parameters of T-cell activity was not demonstrated. We therefore conclude that soluble CD14 in serum is not a useful clinical parameter in establishing disease activity in sarcoidosis. Neopterin and angiotensin-converting enzyme serum concentrations are parameters with higher sensitivity, although specificity remains very low. The exact role of CD14 antigen in sarcoidosis requires further investigation.
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PMID:Evaluation of soluble CD 14 and neopterin as serum parameters of the inflammatory activity of pulmonary sarcoidosis. 128 Apr 95

The major neutralizing epitope on the external glycoprotein of HIV-1 was studied with an envelope-specific monoclonal antibody and with a human serum positive for antibodies to HIV-1 proteins, both of which were able to neutralize virus infectivity. The monoclonal antibody reacted specifically with gp120 from HIV-1IIIB, and was shown to neutralize infection of CEM cells by cell-free virions, and inhibited the formation of syncytia normally observed when uninfected cells are cocultured with HIV-1-infected cells. Similar neutralization of viral infection and inhibition of syncytia formation was also demonstrated by the HIV-1-antibody-positive human serum. By examining a number of overlapping peptides from a region of HIV-1 gp120 known to contain a neutralizing epitope, this epitope was localized between amino acids 307 and 320 (V3 loop) in the external glycoprotein molecule. The monoclonal antibody did not interfere with the binding of gp120 to CD4, or with the subsequent step of CD4-induced shedding of gp120 from the viral envelope. However, it blocked the proteolytic cleavage of the V3 loop by thrombin, suggesting that the antibody may be inhibiting the interaction of the loop with other membrane-bound proteins.
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PMID:Characterization of a neutralizing monoclonal antibody to the external glycoprotein of HIV-1. 128 59

The interaction between the viral envelope protein gp120 and the cellular surface antigen CD4 is a key event in HIV-1 infection. Reciprocal high affinity binding sites have been located in the first domain of CD4 and in the carboxy-terminal region of gp120, respectively. Upon infection, the membranes of the target cells fuse; sites of CD4 and gp120, distinct from their high affinity binding sites, play a role in the post-binding events leading to syncytia formation. We have studied the interactions of CD4 with gp120 and gp120-derived peptides using an in vitro assay based on immobilized recombinant soluble CD4 (sCD4). In this system CD4 binds to recombinant soluble gp120 and to anti-receptor peptides derived from the high affinity CD4-binding site of gp120, as well as to peptides corresponding to the principal neutralizing domain (PND) of the envelope protein, i.e., to the domain required for HIV-1-mediated syncytium formation. Competition experiments performed using epitope-specific mAbs and a variety of peptides indicated that PND-derived peptides are specifically recognized by a CD4 site adjacent to, but distinct from, the high affinity gp120-binding site of CD4. Synthetic peptides patterned on the PND of different viral isolates were retained onto sCD4-based affinity columns at different extent; some of the structural requirements for binding were analyzed. Studies performed on CD4+ T-cells showed that PND-derived peptides also interact with CD4 in its native membrane-bound conformation. These results indicate that a direct contact takes place between CD4 and the gp120 domain participating in HIV-induced syncytia formation.
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PMID:Binding to CD4 of synthetic peptides patterned on the principal neutralizing domain of the HIV-1 envelope protein. 172 May 90

The high-affinity interaction between the envelope glycoprotein (gp120-gp41) of the human immunodeficiency virus type 1 and its receptor, CD4, is important for viral entry into cells and therapeutical approaches based on the soluble form of CD4 (sCD4). Using flow cytometry, we studied the kinetics of binding of sCD4 to gp120-gp41 expressed on the cell surface. sCD4 binding was dependent on sCD4 concentration and temperature and exhibited bimolecular reaction kinetics. Binding was very slow at low sCD4 concentrations (below 0.2 micrograms/ml) and low temperatures (below 13 degrees C) but increased sharply with increasing temperature. The rate constant for association at 37 degrees C (1.5 x 10(5) M-1 s-1) was 14-fold higher than at 4 degrees C, but the affinity of sCD4 to membrane-bound gp120-gp41 was not significantly affected. The activation energy at higher temperatures (28 to 37 degrees C) was less than at lower temperatures (4 to 13 degrees C). After long periods of incubation, we observed a decrease of surface-bound sCD4 and gp120, even at low temperatures, which was attributed to sCD4-induced shedding of gp120. The rate of gp120 shedding was much lower than the rate of sCD4 binding and was dependent on sCD4 concentration and temperature. The finding that sCD4 binding is slow, especially at low sCD4 concentrations, can be of critical importance for efficient blocking of viral infection by sCD4 and should be considered when designing new protocols in the therapy of AIDS patients.
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PMID:Kinetics of soluble CD4 binding to cells expressing human immunodeficiency virus type 1 envelope glycoprotein. 172 75

The mechanism by which glucocorticosteroids (GCS) suppress proliferation of human peripheral blood mononuclear leukocytes (PBML) was investigated. Using the proliferative responses to immobilized anti-CD3 mAb or mitogens (PHA + PMA) as biological readouts, dexamethasone (DEX) and 6 alpha-methylprednisolone (6 alpha-MP) were shown to inhibit PBML proliferation in a concentration-dependent fashion. The mechanism by which GCS mediate immunosuppression did not involve interference with Ca2+ fluxes as: (1) DEX failed to block Ca2+ entry into anti-CD3 + PMA stimulated cells; and (2) Ca2+ ionophores (ionomycin and A23187) failed to circumfent DEX-mediated suppression. DEX also had no effect on protein kinase C (PKC) activity as: (1) inhibitors (H-7 and staurosporin) or stimulators (1,2-dihexanoyl-sn-glycerol [DiC6] and 1,2-dioctanoyl-rac-glycerol [DiC8]) of PKC did not prevent DEX-mediated suppression; (2) DEX did not affect the activation-induced upregulation of CD4 and CD8 expression, an indirect index of PKC activity; and (3) DEX did not alter the activation-associated translocation of PKC from cytosolic to membrane-bound compartments. This, in addition to previous results demonstrating that GCS directly inhibit cytokine gene transcription and that rII-1 + rIL-6 + rIFN-gamma completely abrogated GCS-mediated suppressive effects, further supports the notion that GCS exert their immunosuppressive effects through inhibition of cytokine gene expression.
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PMID:Evidence that glucocorticosteroid-mediated immunosuppressive effects do not involve altering second messenger function. 183 Apr 25

Oligonucleotide uptake was studied in cultured murine spleen and lymph node cells using internally radiolabeled and fluorescein-5-isothiocyanate (FITC)-labeled oligonucleotides. Lymphoid subpopulations were distinguished by flow cytometry and staining with antibodies to cell-surface molecules. Approximately 5% of fresh lymphoid cells take up substantial amounts of oligonucleotide. The percentage of B cells that take up oligonucleotide increased fivefold if cells were cultured for at least 24 hr prior to incubation with labeled oligonucleotides, and increased 10-fold if cells were precultured for 48 hr. T-cell uptake changed very little in culture. Cultured CD4+ and CD8+ T cells had similar oligonucleotide uptake that was less than one-third of that in cultured B cells, but CD4-CD8- T cells had a higher percentage of cells taking up oligonucleotide than did B cells. T- or B-cell mitogens caused markedly increased oligonucleotide uptake in T or B cells, respectively. Oligonucleotide uptake could be inhibited only partially with competitor DNA. To distinguish between cell membrane-bound and intracellular oligonucleotide, cells were washed in acid glycine buffer (which removes most surface oligonucleotide). This demonstrated that most of the oligonucleotide was intracellular. We conclude that oligonucleotide uptake is quite heterogeneous among cultured cells, and that this uptake is inducible by mitogens. These data may be important for the design and interpretation of in vitro experiments, and for the planning of in vivo therapy with antisense oligonucleotides.
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PMID:Uptake of oligodeoxyribonucleotides by lymphoid cells is heterogeneous and inducible. 184 58

We analyzed coexpression of the human immunodeficiency virus type 1 glycoprotein precursor, gp160, and its cellular receptor CD4 in HeLa cells to determine whether the two molecules can interact prior to transport to the cell surface. Results of studies employing coprecipitation, analysis of oligosaccharide processing, and immunocytochemistry showed that newly synthesized CD4 and gp160 form a complex prior to transport from the endoplasmic reticulum (ER). CD4 expressed by itself was transported efficiently from the ER to the cell surface, but the complex of CD4 and gp160 was retained in the ER. This retention of CD4 within the ER is probably a consequence of the very inefficient transport of gp160 itself (R. L. Willey, J. S. Bonifacino, B. J. Potts, M. A. Martin, and R. D. Klausner, Proc. Natl. Acad. Sci. USA 85:9580-9584, 1988). Retention of CD4 in the ER by gp160 may partially explain the down regulation of CD4 in human immunodeficiency virus type 1-infected T cells. Inhibition of CD4 transport appears to be a consequence of the interaction of two membrane-bound molecules, because a complex of CD4 and gp120 (the soluble extracellular domain of gp160) was transported rapidly and efficiently from the ER.
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PMID:CD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor. 221 26

The Class II major histocompatibility molecules are implicated in the initiation of antigen-driven autoimmune responses by CD4-positive T cells. In order to study the structure and function of CD4 and MHC Class II molecules, strategies were developed with the intent of generating secreted forms of these molecules by in vitro mutagenesis of the respective genes. A full length cDNA encoding an expressible human CD4 molecule was mutagenized to introduce a premature stop codon corresponding to residue 367 located 8 amino acids amino terminal to the start of the predicted trans-membrane region. Following DNA-mediated gene transfer of the mutant gene, secreted CD4 was detected in the supernatant of transiently transfected COS-1 cells. Surface expression of the membrane-bound form of CD4 was detected under the same conditions. In an attempt to create a secreted form of the mouse Class II molecule I-Ak the exons encoding the connecting stalk, transmembrane and cytoplasmic domains of both the alpha and beta chains were replaced by the corresponding exons from the gene encoding a secreted Class I-like molecule, Q10b. Transfer of these genes into mouse L cells failed to generate detectable secreted I-A molecules. In view of the secretion of CD4 reported in other mutagenesis studies, it is concluded that very subtle differences in the structure of the COOH-terminus can influence the folding, solubility or transport of the CD4 molecule. In addition, the assembly of heterodimeric Class II molecules may require membrane anchorage of the separate chains or some other contribution from the COOH-terminal domains of the alpha and beta chains.
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PMID:Structure function analysis of in vitro mutated CD4 and major histocompatibility complex class II gene products. 234 62

We have previously shown a novel galactose/N-acetylgalactosamine specific lectin activity (Hodgkin's disease (HD) lectin) on the surface of cultured HD cells (lines L428, its variants, and line L540) to mediate lymphocyte adhesion. We here demonstrate that both surface membrane-bound and secreted HD lectin activities participate in the activation of agglutinated lymphocytes. Among known adhesion molecules expressed by the HD cells, only the intercellular adhesion molecule-1 (ICAM-1) contributed to this activation as an alternative PBL binding site. As yet we have not identified the cellular ligand(s) for the HD lectin on the lymphocyte surface. Pretreatment of lymphocytes with mAb to the accessory molecules CD2, CD3, CD4, CD8, CD11b, or CD11c did not interfere with their response to HD cells. mAb to CD11a (LFA-1), the alleged ligand of ICAM-1, inhibited the ICAM-1 but not the HD lectin-mediated lymphocyte stimulation. Although lymphocyte binding could proceed via either pathway, lymphocyte activation always depended upon factors secreted by the HD cells, one of which we identified as a soluble form of the HD lectin based on its shared properties with the membrane-bound form including immunologic cross-recognition and carbohydrate-binding specificity. Although HD cell-conditioned medium alone stimulated lymphocytes, HD cell plasma membranes could compensate for low concentrations of this medium. In addition, resting lymphocytes, normally unresponsive, were triggered into DNA synthesis by growth medium when cocultured with HD cell membranes. The unique functions of the surface-expressed HD lectin and its soluble counterpart as lymphocyte adhesion molecule and mitogen might be physiologically relevant to the severe immunodeficiencies occurring in patients with HD.
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PMID:Hodgkin's cell lectin, a lymphocyte adhesion molecule and mitogen. 253 Feb 80

T lymphocytes express a tyrosine protein kinase (TPK; protein-tyrosine kinase; ATP:protein-tyrosine O-phosphotransferase, EC 2.7.1.112), pp56lck that is encoded by the lck protooncogene. This TPK was recently found to be associated with the intracellular domain of the T-cell surface glycoproteins, CD4 and CD8, suggesting that it plays an important role in T-cell development and activation. We have studied the regulation of pp56lck and found that this kinase can be rapidly activated by an endogenous mechanism present in T-lymphocyte membranes. This activation was sensitive to sodium orthovanadate and O-phosphotyrosine, consistent with the involvement of a phosphotyrosine phosphatase (PTPase; protein-tyrosine-phosphatase; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) in pp56lck activation. Based on a recent report demonstrating that CD45, the leukocyte common antigen, is a membrane-bound PTPase, we analyzed its role in pp56lck activation. CD45 was found to be the major (greater than 90%) PTPase in membranes of the murine T-lymphoma line BW5147. Moreover, activation of pp56lck was undetectable in a mutant BW5147 line lacking CD45 expression (and the associated PTPase activity). In contrast, activation of pp56lck was readily detected in the wild-type lymphoma line. More important, when immunoprecipitated CD45 was added to pp56lck, the TPK activity of the latter increased greater than 2-fold within minutes. This effect of CD45 was completely blocked by sodium orthovanadate. These findings indicate an important role for the CD45 PTPase in pp56lck activation. This role could be mediated by direct dephosphorylation of a regulatory tyrosine residue in pp56lck.
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PMID:Rapid activation of the T-cell tyrosine protein kinase pp56lck by the CD45 phosphotyrosine phosphatase. 254 4

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