Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human mast cells have been purified from uterine tissues, and their surface marker profile and function have been evaluated as part of ongoing studies of mast cell heterogeneity. Using a panel of antibodies, purified uterine mast cells (UMC; 81% +/- 7% purity, n = 10) were analyzed by immunofluorescence and flow cytometry for surface expression of various antigens. Consistent with previous analyses of mast cells from other tissues, UMC expressed HLA class I, IgE, c-kit receptor, CD9, CD33, CD43, CD45, and CD54, while CD11a, CD11b, CD14, CD16, CD23, and CD64 were not detected. Unlike other mast cells, UMC expressed CD11c/CD18 (p150,95) and CD32 (Fc gamma RII). Additional antigens not previously studied on mast cells included the selectin LECAM-1 (Leu-8) and several beta 1 and beta 3 integrins; expression of very late activation antigen-4 (VLA-4) (CD49d/CD29), VLA-5 (CD49e/CD29), and the vitronectin receptor (CD51/CD61) was seen. Functional studies showed that treatment of human umbilical vein endothelial cells with interleukin-1 (5 ng/mL for 4 hours) resulted in a twofold to threefold increase in adhesiveness for UMC. Purification procedures did not alter histamine release responses to anti-IgE or the calcium ionophore A23187, and treatment of UMC with an anti-CD32 monoclonal antibody (IV.3) did not induce histamine release or alter anti-IgE-induced release. These data suggest that UMC may possess unique phenotypic characteristics, and support the concept of mast cell heterogeneity.
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PMID:Immunophenotyping and functional analysis of purified human uterine mast cells. 137 Jun 42

Human foetal liver cells are an enriched source of mast cell progenitors that complete their differentiation and mature in response to stem cell factor, the ligand for Kit, in liquid culture. These mast cells are Kit+, metachromatic with toluidine blue+, tryptase+, histamine+ and show ultrastructure features of mast cells. Using a panel of monoclonal antibodies (mAb) against different cell-surface antigens (33 mAb were used), the cell-surface phenotype of human stem cell factor-dependent foetal liver-derived mast cells was examined by flow cytometry. Consistent with previous reports on tissue-derived mast cells, those derived from foetal liver in vitro expressed HLA class I, CD9, CD29, CD33, CD43, CD45 and Kit. Unlike mast cells dispersed from tissue, a high expression of CD13 was found. Also, these in vitro-derived mast cells express little, if any, high-affinity IgE receptor. However, small amounts of mRNA for the alpha-chain in foetal liver-derived mast cells compared to KU812 cells (a human basophil-like cell line) could be detected by Northern blotting. Full expression of Fc epsilon RI may require additional growth factor(s).
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PMID:Phenotypic characterization of stem cell factor-dependent human foetal liver-derived mast cells. 768 44

CD43 (leucosialin, sialophorin) is the major sialoprotein of nearly all circulating leucocytes and has important biological activities in cellular differentiation and activation. Recently, the expression of CD43 has also been demonstrated on mast cells and basophils by flow cytometry. In order to further characterize mast cell/basophil leucosialin we have investigated CD43 on the human mast cell line HMC-1, the human basophilic precursor cell line KU-812, and the human promonocytic cell line U-937. The apparent molecular weights (MW) were 123,000 (HMC-1 and KU-812) and 144,000 (U-937) by Western blot analysis. Expression of CD43 on HMC-1 was down-regulated after stimulation with phorbol myristate acetate (PMA). Three monoclonal antibodies (mAb) specific for human CD43 induced homotypic mast cell line (HMC-1) aggregation in a semi-quantitative assay, a phenomenon that has not been described before with mast cells. Monoclonal antibodies specific for seven other surface antigens and an irrelevant mAb of the same isotype had no effect. The level of aggregation was dependent on anti-CD43 mAb concentration, time and temperature. Anti-leucosialin-induced aggregation of HMC-1 cells was completely inhibited by mAb against CD11a (LFA-1) and CD18 (beta 2-chain). Monoclonal antibody to CD54 (ICAM-1) partially inhibited anti-CD43-induced homotypic aggregation, while anti-CD11b (CR3), anti-CD11c (p 150, 95) and a control mAb had no inhibitory effect. We conclude that mast cell line CD43 antigen expression is differentially regulated during cell activation, and speculate that anti-CD43-induced homotypic aggregation of HMC-1 cells is closely associated with modulation of beta 2-integrins.
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PMID:Monoclonal antibodies to leucosialin (CD43) induce homotypic aggregation of the human mast cell line HMC-1: characterization of leucosialin on HMC-1 cells. 783 29

The expression of c-kit and flk-2/flt3 was analyzed in various stages of mast cell differentiation using reverse transcriptase polymerase chain reaction (RT-PCR). Mouse fetal liver cells were sorted using antibodies for Sca-1 (Ly6A/E) and CD43 to obtain a population enriched for early progenitors; committed mast cell progenitors were absent from this population. Mouse fetal liver-derived, IL-3-dependent blast cell colonies provided a source of committed mast cell progenitors, and mast cell colonies provided mature mast cells. Comparison of these populations showed that some uncommitted cells express both c-kit and flk-2/flt3. At the time of commitment to the mast cell lineage, the expression of c-kit increases compared to that of uncommitted progenitors, and the expression of flk-2/flt3 becomes undetectable. Previous studies have shown that steel factor, the ligand for c-kit, supports mast cell differentiation in vivo and in vitro. In contrast, the ligand for flk-2/flt3 is inactive on mast cells. Thus, receptor gene expression appears to be an important determinant of the response or lack of response of mast cells to the ligands for these two homologous receptors.
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PMID:Loss of flk-2/flt3 expression during commitment of multipotent mouse hematopoietic progenitor cells to the mast cell lineage. 921 38

Leukosialin (CD43), the major sialoprotein on circulating leukocytes, has been previously described to be down-regulated on neutrophils following activation with phorbol myristate acetate (PMA). The other single cells previously examined, blood lymphocytes, do not down-regulate CD43 when stimulated by PMA. Recently, we have characterized leukosialin on the human mast cell line HMC-1 and observed that leukosialin is down-regulated after stimulation with PMA. In the present study, we have investigated the mechanism of PMA-mediated down-regulation of CD43 on HMC-1 cells (subclone 5C6). PMA caused the release of soluble leukosialin (123 kD) during HMC-1 cell activation. The molecular weight of soluble leukosialin was nearly identical to that of the cell-membrane bound molecule, suggesting a cleavage proximal from the cell membrane. Inhibitors of serine proteases, like phenylmethylsulphonyl fluoride (PMSF), benzamidine and 3, 4-dichloroisocoumarin, blocked the PMA-mediated cleavage of CD43. In all experiments, the inhibition of CD43-down-regulation was dependent on the concentration of protease inhibitors. Treatment of HMC-1 cells with various proteases (trypsin, alpha-chymotrypsin, elastase, papain, nagarse) substantially decreased anti-CD43 binding capacity and caused the release of soluble leukosialin (116 kD) or its fragments into the supernatant. Pretreatment of HMC-1 cells with neuraminidases from Vibrio cholerae or Arthrobacter ureafaciens resulted in an increased sensitivity of CD43 against proteases, whereas the effects of PMA were not influenced. In conclusion, proteolytic cleavage of CD43 is described for the first time in a cell other than neutrophils, namely HMC-1 cells. Our results suggest that serine proteases are involved in the PMA-mediated down-regulation of leukosialin on HMC-1 cells.
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PMID:Leukosialin (CD43) is proteolytically cleaved from stimulated HMC-1 cells. 924 33

CD43 has been shown to be involved in the regulation of cellular adhesion and activation of leukocytes, but its functional significance for mast cell biology has been poorly defined. We demonstrate here that mAb engagement of surface CD43 on human leukemic (HMC-1) mast cells initiates a signaling cascade which involves protein kinase C, while tyrosine kinases appear to play a minor role, as evidenced by effects of different kinase inhibitors on homotypic aggregation induced via CD43. Furthermore, administration of an activating anti-CD43 mAb is shown to induce and promote TNF-alpha- and to enhance IL-8-secretion from HMC-1 cells, but it does not initiate histamine, tryptase, or LTC4 release, suggesting that the intracellular pathways leading to aggregation and release of certain mast cell mediators are differentially regulated. Additionally, engagement of CD43 on HMC-1 cells leads to down-regulation of CD43 surface expression, implying that CD43 may be potentially involved in its own regulation.
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PMID:Signal transduction via CD43 (leukosialin, sialophorin) and associated biological effects in human mast cell line (HMC-1). 947 99

An autopsy case of systemic mast cell disease (SMCD) without primary skin lesions in a 57-year-old Japanese male is described. Initially the patient was suspected of having liver cirrhosis or malignant lymphoma because of hepatomegaly and lymph node enlargement on admission. However, a lymph node biopsy and bone marrow aspiration conducted on his third admission indicated a SMCD because of the existence of metachromatic cell aggregates stained with toluidine blue. At autopsy, the diagnosis was confirmed because the proliferating cells were histochemically proven to be mast cells by naphthol AS.D chloroacetate esterase, Giemsa and alcian blue, in addition to toluidine blue staining. The intra-abdominal and retroperitoneal lymph nodes were replaced by mast cell aggregates, which caused the splenic infarction and bilateral hydronephrosis, with infiltration of mast cells into the spleen and kidneys also being apparent. Mast cell infiltration was similarly found in the bone marrow, liver, ileum and ascending colon. Immunohistochemically, the mast cells were positive for antibodies of alpha 1-antichymotrypsin, CD45 (LCA), CD43 (MT-1), CD45R (MB-1) and the oncoprotein c-kit. Electron microscopic examination using formalin-fixed tissue gave supportive evidence of a mast cell origin for the lesions.
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PMID:Systemic mast cell disease with splenic infarction: a case report. 970 48

Mast cell disease (MCD) is a rare proliferation that may be easily confused with other hematopoietic tumors. Several paraffin section antibodies immunoreact with mast cells but most are not specific. Tryptase, a specific marker of mast cells, may not be cost-effective to maintain in a laboratory because of the rarity of these lesions. This study was undertaken to assess the immunoreactivity of MCD and attempt to select a limited antibody panel for diagnosing MCD among hematopoietic tumors that morphologically mimic MCD. Immunophenotyping of cutaneous ( 10 cases) and extracutaneous (18 cases) MCD, as well as 94 other hematopoietic neoplasms, was performed on paraffin sections. All cases of MCD showed strong and diffuse positivity for CD68 and tryptase. In the vast majority of the cases, the mast cells were also positive for CD117 (27 of 28) and CD43 (25 of 27). Four cases (40%) of cutaneous MCD demonstrated a subpopulation of mast cells expressing myeloperoxidase (MPX), whereas all extracutaneous MCD were negative for MPX. Two (40%) extramedullary myeloid tumors (EMT) expressed CD43, CD68, CD 117, and MPX, but none expressed tryptase. CD43, CD68, CD117, and tryptase were expressed by 25%, 1%, 15%, and 1%, respectively, of all B-cell lymphoid neoplasms, and none expressed more than one of these four antigens. We conclude that (1) cutaneous MCDs may demonstrate a subpopulation of MPX antigen expressing tumor cells and may be confused with cutaneous involvement by myeloid leukemia if other antibodies are not used; (2) tryptase is the most specific mast cell marker among the antibodies studied; and, (3) the detection of tryptase, together with CD68, CD117, and usually CD43, is unique to MCD among hematopoietic tumors.
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PMID:Paraffin section immunophenotype of cutaneous and extracutaneous mast cell disease: comparison to other hematopoietic neoplasms. 1080 Sep 89

Haptoglobin (Hp) is an acute phase reactant produced by hepatocytes. There is evidence for an immunomodulatory potential of Hp, though there is no clear evidence yet about the mechanisms of this action. We have previously shown that Hp interacts with the beta2-integrin CD11b/CD18. In addition, other investigators reported the binding of Hp to B lymphocytes through the CD22 receptor, and to neutrophils through two different receptors. In the present study, we investigated the interaction of haptoglobin with the human mast cell line HMC-1. We report that fluorescein isothiocyanate (FITC)-labelled haptoglobin binds to this cell line and that binding is increased by calcium in a dose- and time-dependent manner. Hp binding sites on HMC-1 were upregulated upon stimulation with phorbol myristate acetate (PMA)/A23187 and after treatment with anti-CD43 and anti-CD44 monoclonal antibodies (MoAbs). HMC-1 cells do not express either CD11b/CD18 or CD22 receptors, indicating that the haptoglobin-binding receptor on this cell line is different from the known receptors. Assessment of cell function showed that Hp inhibits the spontaneous growth of HMC-1 up till 40% at higher Hp concentrations, but it did not exhibit any effect on the expression of CD54 on the release of either tryptase or IL-1ra. In conclusion, haptoglobin binds specifically to human mast cells via a receptor different from CD11b/CD18 and CD22, and may play a role in the modulation of mast cell functions. Exploration of Hp effects in mast cell-dependent diseases such as allergic rhinitis and urticaria seems warranted.
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PMID:Haptoglobin interacts with the human mast cell line HMC-1 and inhibits its spontaneous proliferation. 1196 16

CD34 is a cell-surface sialomucin expressed by hematopoietic stem cells (HSC), mast cells, and vascular endothelia. Despite its popularity as an HSC marker, the function of CD34 on hematopoietic cells remains enigmatic. Here, we have addressed this issue by examining the behavior of mutant mast cells lacking CD34, the related sialomucin, CD43, or both molecules. Loss of these molecules leads to a gene-dose-dependent increase in mast cell homotypic aggregation with CD34/CD43KOs > CD43KO > CD34KO > wild-type. Importantly, reexpression of CD34 or CD43 in these cells caused reversal of this phenotype. Furthermore, we find that loss of these sialomucins prevents mast cell repopulation and hematopoietic precursor reconstitution in vivo. Our data provide clear-cut evidence for a hematopoietic function for CD34 and suggest that it acts as a negative regulator of cell adhesion.
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PMID:CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution. 1566 58


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