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)

We have produced two lines of transgenic mice in which the expression of temperature-sensitive SV-40 large T antigen is targeted to bone marrow megakaryocytes via the platelet factor 4 (PF4) tissue-specific promoter. The progeny of these transgenic mice were observed for about 3 mo, and no malignancies were detected over this period of time. The offspring of these transgenic mice, 6- to 12-wk of age, served as a source of bone marrow cells, which upon in vitro cultivation at the permissive temperature yielded immortalized cell lines (MegT). At the permissive temperature, MegT cells exhibit the characteristics of early 2N and 4N megakaryocytes which include the presence of specific gene products such as PF4, glycoprotein IIb, acetylcholinesterase, and CD45 as well as the absence of molecular markers of other cell lineages such as the macrophage marker Mac-1, the T helper cell marker CD4, the mast cell marker IgE, the T cell marker CD2 or the erythroid cell marker alpha-globin. The inactivation of the oncogene by a shift of temperature from 34 degrees to 39.5 degrees C produces a reduction in the frequency of the 2N cells, in conjunction with the appearance of 8N and 16N cells, consisting of 27 and 3% of total cells, respectively. Thus, we have generated hematopoietic cell lines that are trapped in the early stages of megakaryocyte commitment, but able to undergo part of the normal program of terminal differentiation.
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PMID:Targeted expression of a conditional oncogene in hematopoietic cells of transgenic mice. 825 49

LAMA-84, a human leucocytic cell line, which upon establishment was described as having megakaryocytic, erythroid and granulocytic characteristics, was analysed for expression of various differentiation markers. In addition to some of the previously described phenotypic characteristics, this cell line was found to express mRNA for several proteins characteristic for basophilic leucocytes and mast cells. The authors show that LAMA-84 cells express mRNA for the mast cell tryptase, the proteoglycan core protein, carboxypeptidase A and the alpha and beta chains of the high affinity IgE receptor (Fc epsilon RI). The authors examined the potential of LAMA-84 to differentiate in serum-free medium or after DMSO or PMA treatment. Depending on the inducing factor, surface expression of the Fc epsilon RI alpha-chain was increased from 20% to 35-50% of the cells and mRNA levels for tryptase were increased in serum-free medium and after DMSO treatment. LAMA-84 was found to express CD13, CDw17, CD29, CD33, CD40, CD45 and CD117. Furthermore, mRNA for the eosinophil/basophil markers Charcot-Leyden crystal (CLC) protein and the major basic protein (MBP), as well as the erythrocyte differentiation marker alpha-globin, was detected. However, the authors observed only trace amounts of mRNA for another erythroid differentiation marker (glycophorin), trace amounts of the megakaryocytic marker GPIIIa, and no detectable level of GPIb alpha. By comparing the expression pattern of a panel of differentiation markers in LAMA-84, and a second human cell line (KU812) expressing a basophil phenotype, it is evident that these cell lines, which presently are the only two cell lines identified with basophilic characteristics, share a large number of phenotypic characteristics.
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PMID:Characterization of a human basophil-like cell line (LAMA-84). 869 92

The case of a 62-year-old man who presented with acute abdominal pain and a widespread tumor involving the retroperitoneum is described. Three weeks after initial presentation, the patient died suddenly of acute cardiac failure with signs of arrhythmia. Autopsy revealed a disseminated tumor with infiltration of the retroperitoneal fat, as well as nodules in the left testis and the right atrium. The tumor cells were reactive for CD45, vimentin, and chloroacetate esterase, but were unreactive with a broad spectrum of antibodies against myelomonocytic and lymphocytic antigens and with antibodies against tryptase and c-kit (CD117), which are characteristic markers for mast cells. However, the bone marrow exhibited the typical picture of mastocytosis, with disseminated clusters of differentiated spindle-shaped cells that stained strongly for tryptase, c-kit, and chloroacetate esterase. No infiltrates of well-differentiated mastocytosis could be detected in any of the extramedullary tissues investigated. A diagnosis of bone marrow mastocytosis with an associated undifferentiated extramedullary tumor of hemopoietic origin was established. By definition, the extramedullary tumor could not be diagnosed as a granulocytic sarcoma or (differentiated) mastocytoma, but the possibility that a mast cell progenitor could be involved in the evolution of both tumors cannot be ruled out.
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PMID:Bone marrow mastocytosis associated with an undifferentiated extramedullary tumor of hemopoietic origin. 914 Mar 15

The immunophenotypic characteristics of both bone marrow (BM) and peripheral blood (PB) mast cells (MC), from a patient suffering from an aggressive systemic mast cell disease (SMCD), were sequentially analyzed by flow cytometry using direct immunofluorescence. Analysis was carried out at diagnosis, during clinical response induced by interferon alfa-2h/prednisone therapy, and later at relapse. Our results show that together with the CD117 and IgE characteristic markers, at diagnosis BM MC showed strong expression of CD11c, CD13, CD29, CD33, CD44, CD45, CD63, and CD71, and they were also positive for CD2, CD22, CD25, and CD54 although at a lower level. PB MC displayed similar immunophenotypic characteristics although they had a lower expression of CD11c, CD25, CD33, CD63, CD69, and CD71 with a higher reactivity for CD117. Unlike BM MC, PB MC were weakly positive for CD41a and CD61. Sequential studies showed decreased numbers of both BM and PB MC during clinical response associated with a higher expression of the CD29 and CD54 adhesion molecules. In turn, clinical relapse was related to increased numbers of PB and BM MC together with lower CD2, CD11c, CD45, and and CD54 expression and a higher reactivity for the CD117 and CD25 antigens. CD2 had become negative at the last follow-up study. In addition, an increased proportion of S-phase MC was observed at relapse. These findings suggest that the assessment of the quantitative expression of cell-adhesion molecules and growth-factor receptors together with cell cycle studies of mast cells could be of value for monitoring therapy and predicting clinical outcome in aggressive SMCD.
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PMID:Sequential immunophenotypic analysis of mast cells in a case of systemic mast cell disease evolving to a mast cell leukemia. 914 16

The case of a 63-year-old man with a widespread retroperitoneal tumor and two tumor nodules in the left testis is described. Histopathological and cytopathological examination of tissue from the retroperitoneal tumor led to a diagnosis of lymphoreticular neoplasia. The patient died in acute cardiac failure, five weeks after initial presentation. Autopsy revealed another tumor nodule in the right atrium. Macroscopically, the bone marrow appeared normal. The tumor cells were reactive for CD45, vimentin and chloroacetate esterase, but were uncreative with a broad spectrum of antibodies against myelomonocytic and lymphocytic antigens and antibodies against tryptase and c-kit (CD117), characteristic markers for mast cells. However, the bone marrow exhibited the typical picture of mastocytosis. A diagnosis of bone marrow mastocytosis with an associated secondary extramedullary mast cell sarcoma was established. The cause of death was heart failure due to arrhythmia caused by an exophytic atrioseptal tumor nodule.
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PMID:[Association of bone marrow mastocytosis with extremely immature extramedullary mast cell sarcoma]. 927 45

CD45 isoform expression patterns were examined in various mast and monocyte cell populations. The reverse transcription-polymerase chain reaction (RT/PCR) and Southern analysis showed these myeloid cells express characteristic sets of CD45 isoforms. Mast cells produce mRNA for two splice variants, one containing exons 5, 7 and 8 of the alternatively expressed exons (therefore lacking exons 4 and 6) and another containing variable exons 7 and 8. Monocytes express three prominent CD45 mRNA species, one which includes exons 5, 7 and 8, another with exons 7 and 8 and the third containing only exon 8 of the variable exons. These results show that there are clear differences within the myeloid lineage sub-populations with respect to CD45 exon usage which appear to delineate mast cell and monocyte specific patterns.
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PMID:Murine mast cells and monocytes express distinctive sets of CD45 isoforms. 956 66

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

The transmembrane tyrosine phosphatase CD45 regulates the activity of src family protein tyrosine kinases (PTK) and thereby influences the signaling via such receptors as T and B cell antigen receptors associated with these PTK. However, its implication in signaling through the mast cell receptor with high affinity for IgE (FcepsilonRI) is less clear, although Lyn, a member of the src family, plays an important role in FcepsilonRI-mediated signaling. To define a role for CD45 in FcepsilonRI signal transduction, we established CD45 high expressing rat basophilic leukemia cell lines (RBL-CD45H) and cell lines expressing trace amounts of CD45 (RBL-CD45L). We demonstrate that although all RBL-CD45L cell lines degranulate following IgE- and antigen-induced FcepsilonRI aggregation, the response is significantly reduced at a low dose of antigen. The cells show a delayed and slowed Ca(2+) mobilization even though at a higher dose where the cells degranulate to a similar extent as RBL-CD45H. This diminished Ca(2+) response is restored by reconstitution of RBL-CD45L with a chimeric molecule containing the cytoplasmic phosphatase domains of rat CD45. Furthermore, tyrosine phosphorylation of FcepsilonRI, association of FcepsilonRI with Lyn and PTK activity associated with FcepsilonRI, all of which are enhanced upon FcepsilonRI aggregation in RBL-CD45H, are impaired in RBL-CD45L. Finally, we show that FcepsilonRI is physically associated with CD45 in RBL-CD45H prior to receptor aggregation. Thus, we propose that, although not indispensable in mast cell degranulation, CD45 positively regulates the signaling through FcepsilonRI by promoting the activation of FcepsilonRI-associated Lyn.
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PMID:Regulation of mast cell signaling through high-affinity IgE receptor by CD45 protein tyrosine phosphatase. 1065 52

Dermal dendrocytes (DDs) are bone marrow-derived cells which are abundant in normal human and murine dermis, where they are closely associated with mast cells in the perivascular space. The biological role of DDs remains enigmatic. DDs express coagulation factor XIIIa and the recently described von Willebrand factor receptor, GPIb alpha, potentially indicating a function in tissue repair and haemostasis, although participation in antigen presentation is also speculated. In healing wounds and 'fibrohistiocytic' tumours, such as dermatofibromas, DDs are often associated with non-dendritic histiocytes, some of which also express factor XIIIa (FXIIIa). We have utilized human skin organ culture to examine the effects of various biological mediators on cytological characteristics of DDs. It was found that by 24 h in organ culture, immunoreactive DDs begin to lose their dendritic shape, assuming more rounded contours. This phenomenon was accentuated by mast cell degranulation; was independent of the nature of mast cell secretagogue; and could not be reproduced by recombinant tumour necrosis factor-alpha, a cytokine known to increase FXIIIa expression in DDs. Like their dendritic precursors, non-dendritic cells expressed variable FXIIIa, CD34 and CD68 and did not express CD1a or CD45. By ultrastructure, non-dendritic cells that develop in vitro resembled non-degenerating monocytes containing occasional primary lysosomes and lipid inclusions, and like DDs, expressed fibronexus-like plaques on the cell membrane. Transition of DDs from dendritic to non-dendritic cells as a consequence of specific microenvironmental influences may provide insight into the frequent concurrence of these two cytological types in fibrohistiocytic tissue reactions and neoplasia.
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PMID:Cytological alterations in dermal dendrocytes in vitro: evidence for transformation to a non-dendritic phenotype. 1088 40

The aim of this study was to determine and to evaluate silica induced lung cell reactivity--if any--in bronchoalveolar space, before clinical changes develop. Bronchoalveolar lavage (BAL) was carried out in 15 nonsmoking individuals with chronic professional silica exposure, free of lung signs and symptoms. Controls were healthy nonsmokers. Routine BAL cytology (HE, MGG) was completed by mast cell staining (toluidine blue). BAL lymphocyte subsets were phenotyped by direct two- and three-color immunofluorescence (applied DAKO A/S monoclonal antibodies: anti-CD3, CD4, CD8, CD11b, CD14, CD15, CD16 + 56, CD19, CD25, CD45, HLA-DR). Parallel staining was performed in peripheral blood. In individuals with chronic silica exposure we found: significant increase in alveolar macrophage (362 +/- 45 vs 160 +/- 33 x 10(3) cells/ml, p < 0.05), lymphocyte (61 +/- 9 vs 24 +/- 5 x 10(3) cells/ml, p < 0.05) and BAL total cell (415 +/- 76 vs 187 +/- 34 x 10(3) cells/ml, p < 0.05) numbers; significant increase in mast cell (0.4 +/- 0.1 vs 0.2 +/- 0.1, p < 0.05), NK cell (7.0 +/- 1.8 vs 3.6 +/- 1.0, p < 0.05) and Th early activated lymphocyte percent (CD4 + CD25+ calculated as percentage of CD4+ cells: 15.1 +/- 1.5 vs 7.8 +/- 1.6, p < 0.01). All results were presented as median +/- SEM. Bronchoalveolar space of people with chronic silica exposure usually shows pathological reaction (especially macrophagic alveolitis), although they are free of manifested pulmonary disease. Th early activated lymphocytes, NK cells and mast cells seem to play important role in the early interstitial lung tissue reaction to silica.
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PMID:[Cytoimmunologic changes in material obtained from bronchoalveolar lavage (BAL) in asymptomatic individuals chronically exposed to silica dust]. 1100 45


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