Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aggregated IgG coupled covalently with bis-diazobenzidine (BDB-IgG) and labeled with 3H-diazobenzene (3H-BDB-IgG) has been used to study the binding of soluble IgG aggregates to human platelets in relationship to the release of the contents of intracellular granules (e.g., serotonin). In washed cell suspensions a minimum of 0.14 to 0.2 mug 3H-BDB-IgG per 5 X 10(8) platelets (40 to 70 aggregates per cell) was required for the triggering of the release reaction and cell aggregation. Binding was independent of divalent cations. The Arrhenius plot gave a straight line between 0 to 37 degrees C and a Q10 of 1.6. Neither inhibitors of the release reaction nor energy metabolism, nor formaldehyde fixation of the platelets affected binding. Bound 3H-BDB-IgG was not significantly eluted by IgG, bovine albumin (BSA), buffer, or plasma. Binding to washed platelets was more strongly inhibited by human IgG than by F(ab')2, bovine IgG, human albumin (HSA), or BSA. Plasma was an even more effective inhibitor of both binding and release. Plasma deficient in IgG or depleted of complement retained its inhibitory capacity. In the presence of plasma, at physiologic ratios of plasma and platelets, no release of serotonin was observed. Binding, although inhibited in rate, nevertheless occurred. It was enhanced by divalent cation chelation and had a Q10 of 2.5. The release reaction of washed platelets to which 3H-BDB-IgG had been bound in the presence of HSA or BSA was also inhibited by the subsequent addition of plasma or plasma proteins (human IgG being more effective than bovine IgG, F(ab')2, HSA, or BSA). 3H-BDB-IgG bound in the presence of either plasma or human IgG did not induce release when the platelets were subsequently suspended in media lacking these proteins. Thus, it appears that the platelet Fc receptor binds 3H-BDB-IgG by a process which is effectively inhibited by plasma, or by free IgG with an intact Fc, and to some extent by high concentrations of other proteins. The effects of bound IgG aggregates are dependent on the other proteins present both during binding and subsequently added. The mechanism of such receptor modulation and its implications in vivo are discussed.
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PMID:Studies of the mechanism of the human platelet release reaction induced by immunologic stimuli. III. Relationship between the binding of soluble IgG aggregates to the Fc receptor and cell response in the presence and absence of plasma. 55 68

Immune guinea pig lymph node cells were fractionated on Ig anti-Ig or HSA anti-HSA affinity columns or on plastic surface in medium containing carbonyl iron. These techniques selectively removed B lymphocytes, K lymphocytes or adherent cells. The residual cells (Fc receptor-negative T lymphocytes) responded to soluble antigen in vitro in the same way or even better compared with nonfractionated cells. In addition, there was no indication that antigen-antibody complexes were superior to antigen in triggering lymph node cells or purified lymph code T lymphocytes into DNA synthesis. The results obtained suggested that memory T lymphocytes can be stimulated by antigen autonomously.
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PMID:Lymphocyte proliferation in vitro induced by soluble protein antigens. II. Cellular requirements. 108 85

Phosphotyrosine-containing proteins were detected by western blotting of whole cell lysates of purified human neutrophils or rat basophilic leukemia cells (RBL-2H3) using a polyclonal anti-phosphotyrosine antibody. When either cell type was stimulated with the appropriate Fc crosslinking agent, heat-aggregated IgG for the neutrophil or DNP-HSA for the IgE-sensitized RBL-2H3, a rapid increase in the phosphotyrosine content of several proteins was observed. The kinetics and specificity of both responses suggest that Fc receptor crosslinking activates a receptor-associated tyrosine kinase, probably a member of the src family of tyrosine protein kinases. The subsequent tyrosine phosphorylation events are likely to be important in Fc receptor-mediated stimulus-response coupling in inflammatory cells.
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PMID:Tyrosine phosphorylation is an early signaling event common to Fc receptor crosslinking in human neutrophils and rat basophilic leukemia cells (RBL-2H3). 171 Apr 46

Several methods for enumeration of Fc receptor bearing T lymphocytes and mononuclear cells from human peripheral blood were compared. The detection of Fc receptors is based on the formation of EA rosettes by using bovine erythrocytes and purified rabbit IgG or IgM antibodies. As alternative method the mixed rosette assay (EA rosettes plus sheep erythrocyte rosettes) (3) was applied for determining TG lymphocytes without the need of T cell separation. Independent of the method used for T cell separation (preparative rosetting with sheep erythrocytes stabilized by AET or HSA) the number of TG and TM lymphocytes was found to be identical. TG values obtained by use of the mixed rosette assay were significant lower (10 +/- 2%) than those obtained with the classical test (18 +/- 5%) (EA rosettes after T cell separation). Obviously this difference is due to a contamination of T lymphocyte preparations by non-T cells. On freshly isolated T lymphocytes without overnight culture we obtained 29% and 35%, respectively TM lymphocytes after separation of T cells using sheep erythrocyte rosettes stabilized with AET or HSA. The expression of FcIgM receptors was found to be strongly dependent on the composition and pH value of the culture medium. In the presence of human AB serum the maximum of FcIgM receptor expression on isolated T cells was obtained at pH 8.5. Under optimum conditions we found 63% and 66% respectively TM lymphocytes after T cell separation using AET or HSA stabilized sheep erythrocytes.
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PMID:[Fc-IgG and Fc-IgM receptor-carrying lymphocytes in human blood. Optimization of determining T(M) lymphocytes]. 295 48

IgG antibodies were found to increase the uptake of circulating dinintrophenylated human serum albumin (DNP-HSA) preparations by the nonparenchymal liver cells in rats. Highly DNP-conjugated HSA was taken up by the Kupffer cells both when given alone and when complexed by IgG. More lightly DNP-conjugated HSA was taken up mainly by the liver endothelial cells. Here, IgG promoted the antigen uptake both by the Kupffer cells and by the endothelial cells. Uptake of IgG immune complexes (IgG-ICs) by the sinusoidal endothelial cells of the liver is a new aspect on the function of these cells. Whether or not this phenomenon is Fc receptor-mediated is discussed. A heat-labile serum factor was found to direct the ICs to the Kupffer cells. This implies that serum complement and hepatic C3 receptors are essential for the physiological clearance of circulating immune complexes.
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PMID:Hepatic uptake of circulating IgG immune complexes. 401 43

We previously postulated that desensitization of human basophils was due to endocytosis or shedding of IgE and/or its Fc receptor. We report here, however, that during a 3-hr desensitization of purified basophils, there was no loss of cell surface antigen-specific IgE. The specific desensitization induced by antigen persists for at least 24 hr whereas simultaneously occurring nonspecific desensitization can recover during the same time interval. Therefore, we suggested that specific desensitization may result from a permanent modification of the Fc receptor or some closely associated protein. On the basis of elution studies of 125I-labeled BPO-HSA, we also suggest the antigen antibody reaction matures to aggregates of increasing size, and we propose that these large aggregates, unable to initiate a release signal, cause an additional component of desensitization.
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PMID:Studies of antigen binding on human basophils. II. Continued expression of antigen-specific IgE during antigen-induced desensitization. 618 51

A soluble immune complex was used as a drug carrier targeted to Fc-receptor-positive cells. Two receptor-positive tumor cell lines, WEHI-3 and M5076, were exposed to methotrexate-human serum albumin conjugate (MTX-HSA) in the presence and absence of anti-HSA antiserum. Both cell types were killed by 30 nM MTX when the drug conjugate was given in the presence of antiserum but were totally unaffected in the absence of antiserum. Drug-free HSA given with antiserum had no effect. Both cell lines responded similarly despite their marked difference in phagocytotic activity. One of the two lines, M5076, is defective in MTX transport and hence resistant to free MTX. Since this line would not be affected by MTX released extracellularly from MTX-HSA, its susceptibility implies that MTX is released inside cells, after endocytosis of the complex, and that endocytosis circumvents the transport defect. Two cell lines lacking Fc receptors (CHO and L929) were not influenced by the drug complex. The pharmacologic effect is mediated by a specific ligand-receptor interaction, since Fc receptor-positive cells are protected by an excess of unconjugated HSA and by the addition of a small amount of staphylococcal protein A, which binds to the Fc portion of IgG. These data demonstrate that Fc receptors can be exploited for cellular drug delivery using a common antigen-antibody complex as a drug carrier.
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PMID:Selective killing of Fc-receptor-bearing tumor cells through endocytosis of a drug-carrying immune complex. 636 28

To evaluate the feasibility of using a monoclonal anti-Fc receptor antibody to alter Fc receptor function in vivo, the disappearance of radiolabeled human serum albumin-rabbit anti-human serum albumin (HSA-anti-HSA) complexes was studied in mice before and after the infusion of 2.4G2, a monoclonal antibody (developed by J. Unkeless). 2.4G2 specifically binds to Fc receptors on mouse macrophages. Under standardized conditions, 6.1% of an i.v. administered dose of anti-HSA was sequestered in the liver of B6/D2J mice. When HSA-anti-HSA complexes were administered, 53.4% were sequestered. If 8 micrograms/g body weight of 2.4G2 was infused i.p. 1.5 hr before HSA-anti-HSA, only 13.7% of the infused complexes were sequestered in the liver. The inhibition in Fc receptor-mediated sequestration produced by this dose of antibody persisted for at least 24 hr. A dose of 1 to 2 micrograms/g was sufficient to inhibit sequestration by 50%. Animals receiving daily injections of 2.4G2 cleared immune complexes from their blood much more slowly than untreated animals. Because 2.4G2 was not cytotoxic to peritoneal macrophages in vitro in the presence of serum, and because comparable inhibition of Fc receptor function was observed in vivo in C5-deficient mice, blockade of function does not depend upon complement-mediated lysis of macrophages. The maximal degree of inhibition of Fc receptor function obtained by using intact 2.4G2 was about twice that observed by using Fab fragments of 2.4G2 to block receptors. In addition to its effect on Fc receptor function, 2.4G2 also had a small but significant inhibitory effect upon the clearance of 125I-labeled heat-aggregated HSA by the mononuclear phagocyte system both in intact and C5-deficient mice. We conclude that 2.4G2 is a potent inhibitor of IgG Fc receptor-mediated immune clearance in vivo.
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PMID:The blockade of Fc receptor-mediated clearance of immune complexes in vivo by a monoclonal antibody (2.4G2) directed against Fc receptors on murine leukocytes. 673 48

Four thymic epithelial cell lines (TEC) were derived from neonatal CBA and non-obese diabetic (NOD) mouse thymus. From these cell lines a series of clones were produced by limit dilution and these have remained in stable culture for more than 1 year. Morphological characterization indicates that most cells are stellate with numerous short or long processes and ultrastructural studies show both active and quiescent cells with junctional complexes and bundles of tonofibrils. Immunohistochemical and flow cytometric analyses show that the cells express cytokeratin and appear to label for markers characteristic of cortical epithelial cells. Most clones express Thy-1, Pgp-1, ICAM-1, HSA and B220 antigen, but are negative for LFA-1, CD2, Mel 14, Fc receptor, Mac-1, CD4 and CD8. All clones express low to moderate levels of class I MHC but are either negative or extremely low for class II MHC antigen. Most clones secrete IL-6 and granulocyte-macrophage-CSF (GM-CSF) in vitro, but generally do not produce IL-2, IL-3, IL-4 or IFN-gamma.
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PMID:Production and characterization of mouse thymic epithelial cell clones. 751 33

Bispecific monoclonal antibody (bsMAb), secreted by hybrid-hybridoma, has an intact 1g molecule construction with dual antigen binding specificities. bsMAb has several advantages over conventional conjugate in tumor targeting therapy: (1) The damage to both antibody and tumoricidal agents due to chemical crosslinking can be avoided. (2) The antigen modulation can be decreased due to monovalence binding of bsMAb with target antigen. (3) The binding affinity between Fc fragment of bsMAb with heterogenous heavy chains and Fc receptor is decreased, so that nonspecific distribution and side effects can be reduced. (4) The bsMAb can pretarget to tumor site, increasing the T/NT ratio and cytotoxicity. In the present study, A bsMAb with versatile adaptor was designed. In this bsMAb, one arm could react with gastric cancer-associated antigen, and the other with a hapten TNP. The bsMAb could mediate different tumoricidal agents crosslinked to TNP. A variant hybridoma 3H11-HAT(s) secreting McAb against gastric cancer was fused with spleen cells of mice immunized with KLH-TNP. After screening and subcloning, 10 hybrid-hybridomas were obtained, which secreted antibodies against both gastric cancer target cells BGC823 and BSA-TNP. By using special bridge method, only hybrid-hybridomas 6A3 (gamma 2b, mu), and 1G7 (gamma 2b, gamma 2b) were confirmed to secrete bsMAb. Further experiments showed that the bsMAb 6A3 and 1G7 could mediate different cytotoxicities, for example, Ricin-TNP, MMC-HSA-TNP and ADM-BSA-TNP. This system is useful for evaluating different tumoricidal agents in bsMAb targeting therapy, and has potential value in clinics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A bispecific monoclonal antibody with versatile adaptor mediating different cytotoxicities]. 792 69


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