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)

The pathogenesis of anaphylactic shock is not completely understood. Mast cell degranulation products may stimulate endothelial cells, leading to activation of fibrinolytic and coagulation systems. We investigated the activation of these systems in insect-sting anaphylaxis. Fifty-five patients with a previous insect-sting anaphylactic reaction and 8 volunteers were challenged with an in-hospital sting. Plasma levels of von Willebrand factor (vWF), coagulation, and fibrinolytic parameters were assessed. After the sting challenge, 20 patients developed anaphylactic symptoms, 7 of whom developed hypotension. In only these 7 patients, but not in the volunteers or in the other patients with no or mild anaphylactic symptoms, vWF levels increased from 107% +/- 33% (mean +/- SD) before, to 235% +/- 134% 60 minutes after the onset of clinical symptoms. This increase of vWF was accompanied by an increase of circulating tissue-type plasminogen-activator (tPA) levels from 5 +/- 3 micrograms/L to 50 +/- 59 micrograms/L and of plasminogen-alpha 2-antiplasmin complex (PAP-c) levels from 6 +/- 3 nmol/L to 297 +/- 225 nmol/L. Both tPA and PAP-c levels peaked 5 minutes after the onset of clinical symptoms. Such increases of tPA and PAP-c were not observed in the volunteers or in the patients who did not develop shock. The increase of tPA and PAP-c levels in the hypotensive patients correlated positively with the degree of mast cell degranulation and inversely with the mean arterial pressure. We conclude that activation of plasminogen may be involved in the pathogenesis of anaphylactic shock induced by insect venom.
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PMID:Controlled insect-sting challenge in 55 patients: correlation between activation of plasminogen and the development of anaphylactic shock. 769 Dec 34

Although mast cells are hematopoietic cells, little is known about the origin of their precursors in vivo. In this study, the origin (donor v recipient genotype) of human mast cells (MCs) was analyzed in a patient who underwent allogeneic bone marrow transplantation (BMT). The patient presented with secondary acute myeloid leukemia (French-American-British classification, M2) arising from refractory anemia with excess of blast cells and bone marrow (BM) mastocytosis. Transplantation was performed in chemotherapy-induced complete remission. On days 88, 126, 198, and 494 after BMT, mast cells were enriched to homogeneity from bone marrow mononuclear cells (BM MNCs) by cell sorting for CD117+/CD34- cells. Purified mast cell populations were CD117(c-kit)+ (> 95%), CD34- (< 1%), CD3- (< 1%), CD14- (< 1%), and virtually free of contaminating cells as assessed by Giemsa staining. The genotype of MCs was analyzed after amplification by polymerase chain reaction (PCR) of a variable number tandem repeat (VNTR) region within intron 40 of the von Willebrand factor (vWF) gene. Unexpectedly, on days 88 and 126 after BMT, sorted MCs displayed recipient genotype as shown by vWF.VNTR-PCR. However, on days 198 and 494, PCR analysis showed a switch to donor genotype in isolated mast cells. Peripheral blood (PB) and BM MNC as well as highly enriched (sorted) CD3+ T cells (PB, BM), CD4+ helper T cells (PB), CD8+ T cells (PB), CD19+ B cells (PB), CD14+ monocytes (PB, BM), and CD34+ precursor cells (BM) showed donor genotype throughout the observation period. Together, these results provide evidence that human MCs developed in vivo from transplanted hematopoietic stem cells. Engraftment and in vivo differentiation of MCs from early hematopoietic progenitor cells may be a prolonged process.
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PMID:Origin of human mast cells: development from transplanted hematopoietic stem cells after allogeneic bone marrow transplantation. 794 67

10,090 dissections of dogs exhibited 2631 neoplastic processes of which 309 involved the heart in the form of eu- and heteropic tumours. The most common primary and/or secondary heart tumour type was hemangiosarcoma (n = 187), followed by paraganglioma (n = 46), carcinoma (n = 33), malignant lymphoma (n = 12), thyroid heart base tumour (n = 9), melanoma (n = 7), mast cell tumour (n = 3) and blastoma (n = 2). The tumour diagnoses were immunohistochemically proved by various antibodies to cytokeratins, vimentin, GFAP, NSE, von Willebrand factor, CD3, CD45RA, S100, thyroglobulin as well as histochemically with argyrophilic, Fontana-Masson and heterochromatic reactions. The odds ratio (OR) for breed and tumour prevalences were determined: German shepherds showed the highest OR for hemangiosarcomas and boxers for paragangliomas.
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PMID:Systemic, metastatic, eu- and heterotope tumours of the heart in necropsied dogs. 869 31

Dietary copper has long been known to be essential for cardiovascular homeostasis. However, the role of copper and cuproenzymes in the normal control of vascular physiology is not well understood. Most studies in the cardiovascular system have focused on copper deficiency-induced defects in the heart or large vessels. Recently, attention has also focused on the effects of copper deficiency in the microcirculation or the small blood vessels that control blood flow, nutrient and waste exchange, and peripheral vascular resistance. Studies in the microcirculation demonstrate that copper is important in mechanisms of macromolecular leakage, platelet-endothelial interactions and vascular smooth muscle reactivity. There is a significantly greater leakage of proteins from postcapillary venules in copper-deficient rats in response to mast cell-released histamine. This response appears to be the result of increased numbers of mast cells and thereby increased available histamine. Copper deficiency also causes an inhibition of in vivo thrombogenesis, which appears to be related to an inhibition of platelet adhesion. Subsequent studies have demonstrated that this is probably caused by a diminished concentration of the adhesion molecule von Willebrand factor. Nitric oxide (NO)-mediated arteriole vasodilation is also compromised in copper-deficient rats. This functional deficit to NO can be reversed by the addition of Cu, Zn-superoxide dismutase (SOD), suggesting that degradation of NO by superoxide anion occurs during copper deprivation. These observations demonstrate that dietary copper is necessary for several microvascular control mechanisms affecting inflammation, microhemostasis and regulation of peripheral blood flow.
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PMID:Dietary copper in the physiology of the microcirculation. 940 74

GPIb alpha, a glycoprotein component of the GPIb-IX-V complex, serves as a platelet membrane receptor that mediates adhesion to von Willebrand factor normally present in the vascular subendothelium. Recent data have demonstrated that GPIb alpha is not restricted to platelets, but is also expressed by endothelium in vitro. In this study, we describe the expression and distribution of GPIb alpha in normal adult and neonatal human skin. GPIb alpha is present, as detected by immunohistochemistry, on endothelial cells and on highly dendritic cells localized within the perivascular space, dermal-epidermal junction, and reticular dermis. By dual-labeling immunofluorescence and confocal microscopy, GPIb alpha-positive cells within the dermal interstitium are demonstrated to represent factor XIIIa-positive dermal dendrocytes. In organ cultures of neonatal human foreskin, mast cell degranulation induced by either substance P or compound 48/80 resulted in transiently increased GPIb alpha expression by dermal dendrocytes. Because the GPIb-IX-V complex plays a part in regulating hemostasis and may be important for cellular interactions with extracellular matrix molecules, these data provide additional insight into the potential function of FXIIIa-positive dermal dendrocytes in skin remodeling and repair.
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PMID:Von Willebrand factor receptor GPIb alpha is expressed by human factor XIIIa-positive dermal dendrocytes and is upregulated by mast cell degranulation. 1046 16

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

Mast cells accumulate within solid tumors and can release many angiogenic factors, suggesting that they may modulate vascularization of tumors. Stem cell factor (SCF) stimulates mast cell migration, proliferation, and degranulation and therefore may influence mast cell behavior within tumors. We investigated the contribution of SCF to tumor angiogenesis by manipulating its level in mammary tumors. Sense or antisense cDNA fragments of rat SCF were ligated into an episomal expression vector. Ethylnitrosourea-induced rat mammary tumor cell lines were transfected with vector containing either control (no insert, C-P), sense (S-P), or antisense (AS-P) SCF DNA. The functional nature of the transfectants was confirmed by measuring SCF in cell lysates and conditioned media. Immunohistochemical analysis of the tumors induced in Berlin-Druckrey rats by these transfected cells demonstrated that mast cell number and microvascular density were significantly higher in S-P tumors and significantly lower in AS-P tumors, compared with C-P tumors. The expression of von Willebrand factor, an endothelial cell marker, showed a similar pattern. AS-P tumors were significantly smaller than either C-P or S-P tumors. These data suggest that SCF modulates tumor growth and angiogenesis via the involvement of mast cells.
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PMID:Modulation of tumor angiogenesis by stem cell factor. 1111 63

During pregnancy, it is essential that sufficient nutrients are supplied by the vascular system to support the dramatic modifications of the rat uterine cervix. Angiogenesis refers to the growth of new blood vessels from pre-existing microcirculation and mast cells have been associated with this process. This study examined the modifications of the vascular compartment and the distribution of mast cells on cervical tissue during pregnancy. Using disodium cromoglycate as a mast cell stabilizer, we determined the effects of the mast cell degranulation on cervical angiogenesis. Mast cell distribution and their degranulation status were evaluated by immunohistochemistry. Endothelial cell proliferation was measured by bromodeoxyuridine incorporation. Vascular areas (absolute and relative) and maturation indices were assessed by quantitative immunohistochemistry of von Willebrand factor and alpha-smooth muscle actin respectively. Mast cells were predominantly observed during the first half of pregnancy in the perivascular zones. The values of bromodeoxyuridine incorporation, absolute vascular area and vascular maturation index exhibited a significant increase throughout pregnancy. All animals that received mast cell stabilizer showed more than 40% of non-degranulated mast cells. Treated rats exhibited a decrease in endothelial proliferation and in relative vascular area; in addition, a large proportion of mature blood vessels was observed, suggesting a diminished level of new vessel formation. The effects of the mast cell stabilizer were sustained beyond the end of treatment. This is the first report that brings evidence that mast cell degranulation could be a necessary process to contribute to the normal angiogenesis of the rat cervix during pregnancy. Further investigations are needed to elucidate the possible implications of abnormal vascular development of the uterine cervix on the physiological process of ripening and parturition.
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PMID:Mast cells degranulation affects angiogenesis in the rat uterine cervix during pregnancy. 1501 57

Integrin alphaIIb, a well-known marker of megakaryocyte-platelet lineage, has been recently recognized on hemopoietic progenitors. We now demonstrate that integrin alphaIIbbeta3 is highly expressed on mouse and human mast cells including mouse bone marrow-derived mast cells, peritoneal mast cells, and human cord blood-derived mast cells, and that its binding to extracellular matrix proteins leads to enhancement of biological functions of mast cells in concert with various stimuli. With exposure to various stimuli, including cross-linking of FcepsilonRI and stem cell factor, mast cells adhered to extracellular matrix proteins such as fibrinogen and von Willebrand factor in an integrin alphaIIbbeta3-dependent manner. In addition, the binding of mast cells to fibrinogen enhanced proliferation, cytokine production, and migration and induced uptake of soluble fibrinogen in response to stem cell factor stimulation, implicating integrin alphaIIbbeta3 in a variety of mast cell functions. In conclusion, mouse and human mast cells express functional integrin alphaIIbbeta3.
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PMID:Integrin alphaIIbbeta3 induces the adhesion and activation of mast cells through interaction with fibrinogen. 1636 95

Integrin alpha IIb beta 3 is expressed in mast cells as well as in megakaryocytes/platelets. A recent study has shown that surface expression levels of integrin alpha V beta 3 are elevated in integrin alpha IIb-deficient bone marrow-derived mast cells (BMMCs) as compared with wild-type (WT) counterparts, but the underlying mechanism remains obscure. Here we demonstrate by transducing integrin alpha IIb into integrin alpha IIb-deficient BMMCs that surface expression levels of integrin alpha V beta 3 are inversely related to those of integrin alpha IIb beta 3. Thus, competitive association of integrin beta 3 with integrin alpha IIb or integrin alpha V determines surface expression levels of integrin alpha IIb beta 3 or alpha V beta 3 in mast cells. We compared WT and integrin alpha IIb-deficient BMMCs as well as integrin alpha IIb-deficient BMMCs transduced with integrin alpha IIb(WT) or non-functional alpha IIb(D163A) mutant and found that enhancement of proliferation, degranulation, cytokine production, and migration of BMMCs through interaction with fibrinogen (FB) depended on integrin alpha IIb beta 3. In addition, elevated surface expression of integrin alpha V beta 3 failed to compensate for loss of FB-associated functions in integrin alpha IIb-deficient BMMCs while enhancing adhesion to vitronectin or von Willebrand factor. Importantly, integrin alpha IIb deficiency strongly suppressed chronic inflammation with the remarkable increase of mast cells induced by continuous intraperitoneal administration of FB, although it did not affect acute allergic responses or mast cell numbers in tissues in steady states. Interestingly, soluble FB promoted cytokine production of BMMCs in response to Staphylococcus aureus with FB-binding capacity, through integrin alpha IIb beta 3-dependent recognition of this pathogen. Collectively, integrin alpha IIb beta 3 in mast cells plays an important part in FB-associated, chronic inflammation and innate immune responses.
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PMID:Evidence that integrin alpha IIb beta 3-dependent interaction of mast cells with fibrinogen exacerbates chronic inflammation. 1975 24


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