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)

Aspirin therapy for patients with systemic mast cell disease (SMCD) decreases the production of prostaglandin D2, which is thought to be a major mediator of flushing. Paradoxically, in 5 to 10% of patients with SMCD, administration of aspirin causes massive mediator release and an anaphylactoid reaction. We attempted aspirin desensitization in a 34-year-old man with SMCD (confirmed by bone marrow biopsy) who was incapacitated by severe flushing episodes and hypotension. His baseline mediator levels of plasma calcitonin, urinary histamine, and urinary N-methyl-imidazoleacetic acid were abnormal. Pentagastrin stimulation increased the plasma level of calcitonin from 47 pg/mL to 130 pg/mL (normal, less than or equal to 110) at 5 minutes. Oral aspirin desensitization was begun; however, after a cumulative dose of 620 mg, an anaphylactoid reaction ensued in conjunction with hypotension, abdominal cramping, and flushing. Coincidentally, 1 hour after the episode, the plasma calcitonin level increased from 37 pg/mL to 540 pg/mL, and the serum tryptase level increased from 1 ng/mL to 3.9 ng/mL. Six hours after the episode, the urine level of histamine increased from 90 micrograms/g creatinine to 337 micrograms/g creatinine, and the urinary N-methylimidazoleacetic acid increased from 32 mg/24 h to 81 mg/24 h. Hence, the patient had increased basal levels of plasma calcitonin that increased substantially during aspirin desensitization and increased to above the upper limit of normal during pentagastrin stimulation. Human mast cells may be capable of producing calcitonin or causing secretion of calcitonin in response to skeletal changes.
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PMID:Increased plasma calcitonin levels in systemic mast cell disease. 793 97

Prostaglandin (PG)D2 is a major product of arachidonic acid metabolism in pulmonary mast cells. We therefore attempted to determine whether measurement of the stable urinary metabolite of PGD2, 9 alpha, 11 beta-PGF2, could serve as a marker of mast cell activation in the lungs. A commercially available enzyme immunoassay was validated and found to be specific and sensitive when applied to unpurified urine. There was no diurnal variation in the levels of 9 alpha, 11 beta-PGF2 in healthy volunteers. Morning baseline values of urinary 9 alpha, 11 beta-PGF2 were measured in three groups--healthy volunteers (n = 9), patients with atopic asthma (n = 14), and aspirin-intolerant patients with asthma (n = 12)--and found to be very similar, 54 +/- 9, 62 +/- 6, and 71 +/- 15 ng/mmol creatinine, respectively (means +/- SEM). Urinary excretion of 9 alpha, 11 beta-PGF2 was increased threefold immediately after allergen-induced bronchoconstriction in nine patients with atopic asthma. Bronchial challenge with inhaled lysine aspirin in eight aspirin-intolerant patients with asthma produced bronchoconstriction without extrapulmonary symptoms and was also followed by a significant increase in the urinary excretion of 9 alpha, 11 beta-PGF2. In addition, challenge with a higher dose of aspirin produced an even greater increase in urinary 9 alpha, 11 beta-PGF2, supporting dose-dependent release of PGD2 during aspirin-induced bronchoconstriction. In contrast, the postchallenge levels of urinary 9 alpha, 11 beta-PGF2 were not increased when bronchoconstriction was induced by histamine challenge in the aspirin-intolerant patients with asthma. The study confirms mast cell involvement in allergen-induced bronchoconstriction and provides novel data, which strongly support the hypothesis that pulmonary mast cells are activated during aspirin-induced airway obstruction. It is finally suggested that measurement of urinary 9 alpha, 11 beta-PGF2 with enzyme immunoassay may be used as a new noninvasive strategy to monitor mast cell activation in vivo.
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PMID:Increased urinary excretion of the prostaglandin D2 metabolite 9 alpha, 11 beta-prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction. 875 20

Mast cells are involved in chronic inflammation and tissue fibrosis. To determine whether these cells are also involved in tubulointerstitial injury in glomerulonephritis, we assayed mast cell infiltration in the kidneys of 107 patients with primary or secondary glomerulonephritis. Using a monoclonal antihuman tryptase antibody, we detected mast cells in the renal cortical tubulointerstitium, the periglomerular areas, and the medullary interstitium, but not in glomeruli. Renal cortical tubulointerstitial mast cells, including periglomerular area, were estimated as 0.8+/-1.6 cells/mm2 in minimal change nephrotic syndrome (n=7), 1.5+/-0.7 cells/mm2 in minor glomerular abnormalities without nephrotic syndrome (n=7), 6.5+/-7.7 cells/mm2 in membranous nephropathy(n=10), 12.9+/-15.5 cells/mm2 in lupus nephritis (n=15), 13.4+/-8.3 cells/mm2 in focal segmental glomerular sclerosis (n=6), 18.5+/-21.1 cells/mm2 in ANCA-related nephropathy (n=5), 19.8+/-14.2 cells/mm2 in membranoproliferative glomerulonephritis (n=5), 21.3+/-17.7 cells/mm2 in immunoglobulin A (IgA) nephropathy (n=42), and 33.0+/-33.8 cells/mm2 in diabetic nephropathy (n=10). Except for patients with the rapidly progressive glomerulonephritic syndrome (RPGN), the number of infiltrating mast cells significantly correlated with the serum concentration of creatinine at the time of renal biopsy (r=0.59; P < 0.0001) and with the intensity of tubulointerstitial injury as measured by leukocyte infiltration (r=0.72; P < 0.0001) and fibrosis (r=0.75; P < 0.0001). In contrast, mast cell infiltration did not correlate with urinary protein excretion. In relation to serum creatinine concentration, the number of mast cells was fewer in patients with RPGN than in those with chronic glomerulonephritis. These data suggest that mast cells may contribute to the renal deterioration in glomerulonephritis by inducing chronic tubulointerstitial injury.
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PMID:Tubulointerstitial mast cell infiltration in glomerulonephritis. 977 20

Renal interstitial fibrosis is the final common pathway leading to end-stage renal disease in various nephropathies including renal amyloidosis. However, the role of mast cells (MCs) in the fibrotic process of renal amyloidosis is not fully understood. We compared the distribution of MCs in renal biopsies from 30 patients with AA type renal amyloidosis and 20 control cases. Immunoreactivity of renal MCs to anti-tryptase and anti-chymase was studied. Interstitial myofibroblasts were stained with anti-alpha-smooth muscle actin (alpha-SMA) antibody, and inflammatory cells were identified by anti-CD45, -CD20, and -CD68 mAbs. Positively stained cells were counted, and the relative interstitial and fractional areas of anti-alpha-SMA stained cells were measured. Anti-CD29 mAb was used to detect beta1 integrin and anti-basic fibroblast growth factor (bFGF) mAb for the growth factor on MCs. MCs were rarely found in control samples. In contrast, samples showing amyloid deposition contained numerous tryptase-positive (MCT) (940.17 +/- 5.4 versus 6.74 +/- 1.1/mm2) but fewer chymase-positive (MCTC) cells (20.7 +/- 2.86 versus 1.7 +/- 0.76/mm2) in the renal interstitium. There was a significant relationship between interstitial MCT and creatinine clearance (r = -0.72), and between interstitial MCT and glomerular amyloid-index (GAI) (r = 0.723) and interstitial amyloid area (r = 0.824). Accumulation of MCs correlated significantly with the number of T lymphocytes (MCT: r = 0.694). There was also a significant relationship between mast cell (MC) number and the fractional area of alpha-SMA positive interstitium (r = 0.733) and interstitial fibrotic area (r = 0.6). Double immunostaining demonstrated intracytoplasmic presence of beta1 integrin on 87% of MCT and correlated significantly with the interstitial amyloid area (r = 0.818, P = .001) and T-cell number (r = 0.639, P = .002). bFGF was also detected on 85.5% of MCTC correlating well with the interstitial alpha-SMA-area (r = 0.789). Our results indicate that MCs constitute an integral part of the overall inflammatory process and play a crucial role in interstitial fibrosis in renal amyloidosis.
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PMID:Increased density of interstitial mast cells in amyloid A renal amyloidosis. 1100 43

Fourteen renal biopsy specimens from patients with mesangiocapillary glomerulonephritis type I (MCGN-I) for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available were examined quantitatively. As a control 10 biopsy specimens of kidneys removed because of trauma were used. Morphometric investigations were performed by means of a computer image analysis system to evaluate whether mast cells have a role in tubulointerstitial fibrosis in MCGN-I and to examine the relationship between mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression as well as interstitial infiltrates. The morphometric study revealed that the mean values of the interstitial tryptase positive cells, expression of alpha-SMA, interstitial volume, CD 68+, CD 45RB+, CD 43+ and CD 20+ cells were significantly increased in MCGN-I patients in comparison with control group. In MCGN-I group there were significant positive correlations between interstitial tryptase positive cells and interstitial expression of alpha-SMA, interstitial volume, serum creatinine as well as CD 43+ and CD 68+ cells. The correlations between interstitial tryptase positive cells and CD 45+, as well as CD 20+ cells did not reach statistical significance. In conclusion, our findings demonstrate that mast cells are one of the constitutive cell types in the interstitium in MCGN-I. Additionally, significant positive correlations between interstitial mast cell count and relative interstitial volume as well as serum creatinine concentration suggest the role of these cells in the development of interstitial fibrosis which may contribute to the renal deterioration in patients with MCGN-I.
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PMID:Quantitative analysis of the interstitial mast cells in idiopathic mesangiocapillary glomerulonephritis type I. 1147 6

Eleven renal biopsy specimens from patients with lupus membranous glomerulopathy (LMGN) and 16 from patients with primary (nonlupus) membranous glomerulopathy (NLMGN) for whom light, electron microscopy and immunofluorescence microscopy, and full clinical data were available were examined quantitatively. As a control 10 biopsy specimens of the kidneys removed because of trauma were used. Morphometric investigations were performed by means of a computer image analysis system to evaluate whether mast cells have a role in tubulointerstitial fibrosis in lupus and nonlupus membranous glomerulopathy and to examine the relationship between mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression as well as interstitial infiltrates. The morphometric study revealed that the mean values of interstitial tryptase positive cells, expression of alpha-SMA, interstitial volume, CD68+, CD45RB+, CD43+ and CD20+ cells were significantly increased in LMGN as compared with NLMGN. In both LMGN and NLMGN groups there were significant positive correlations between interstitial tryptase positive cells and interstitial expression of alpha-SMA, interstitial volume, serum creatinine as well as CD68+ cells. The present data suggest that in cases of membranous glomerulopathy with a large number of interstitial mast cells systemic lupus erythematosus should be taken into consideration, even if this aetiology was not clinically suggested at the time of biopsy. Additionally, in both LMGN and NLMGN significant positive correlations between interstitial mast cell count and relative interstitial volume support the role of these cells in the development of interstitial fibrosis, however this relationship needs further investigations.
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PMID:Quantitative analysis of interstitial mast cells in lupus and non-lupus membranous glomerulopathy. 1191 83

Thirty-seven patients with mastocytosis and unexplained elevated levels of urinary N-methylhistamine who were undergoing bone marrow biopsy were studied with respect to the diagnosis of mastocytosis and the manifestations of the disease. These patients were from a group of 66 patients from whom a bone marrow biopsy was obtained and urinary N-methylhistamine levels were measured in the period 1990-1998. In seven (19%) of the 37 patients, mastocytosis was limited to the skin. Five (14%) of the 37 patients showed accumulation of mast cells in the bone marrow without characteristic skin lesions, whereas seven (19%) of the 37 patients showed increased numbers of mast cells both in the skin and the bone marrow. Eighteen (49%) of the 37 patients with elevated N-methylhistamine did not have mast cell accumulation in either the skin or the bone marrow biopsy. The median level of N-methylhistamine in the urine of patients with mastocytosis limited to the skin was 245 micro mol/mol creatinine. The average level of N-methylhistamine was 509 micro mol/mol creatinine in patients with mast cell accumulation in the bone marrow and cutaneous mastocytosis. There was a significant difference in the levels of N-methylhistamine in patients with mast cell accumulation in the bone marrow biopsy compared with those without. The likelihood of mastocytosis with mast cell accumulation in the bone marrow biopsy at a given level of N-methylhistamine was calculated. It was established that an N-methylhistamine level of 297 micro mol/mol creatinine or higher may be considered as a threshold indicator for obtaining a bone marrow biopsy in patients suspected of mastocytosis with mast cell accumulation in the bone marrow. For practical purposes, we propose to consider the cut-off level of approximately 300 micro mol/mol N-methylhistamine creatinine for this assay.
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PMID:Urinary N-methylhistamine as an indicator of bone marrow involvement in mastocytosis. 1237 95

The aim of this study was to investigate if mannitol inhalation, as a model of exercise-induced bronchoconstriction (EIB), causes mast cell activation and release of mediators of bronchoconstriction. Urinary excretion of previously identified mediators of EIB was investigated in association with mannitol-induced bronchoconstriction. Twelve asthmatic and nine nonasthmatic subjects inhaled mannitol and urine was collected 60 min before and for 90 min after challenge. The urinary concentrations of leukotriene (LT)E4, the prostaglandin (PG)D2 metabolite and the mast cell marker 9alpha,11beta-PGF2 were measured by enzyme immunoassay. N(tau)-methylhistamine was measured by radioimmunoassay. In asthmatic subjects, inhalation of a mean+/-SEM dose of 272+/-56 mg mannitol induced a reduction in forced expiratory volume in one second (FEV1) of 34.5+/-2.1%. This was associated with increases in urinary 9alpha,11beta-PGF2 (91.9+/-8.2 versus 66.9+/-6.6 ng x mmol creatinine(-1), peak versus baseline) and LTE4 (51.3+/-7.5 versus 32.9+/-4.7). In nonasthmatic subjects, the reduction in FEV1 was 1.0+/-0.5% after inhaling 635 mg of mannitol. Although smaller than in the asthmatics, significant increases of urinary 9alpha,11beta-PGF2 (68.4+/-6.9 versus 56.0+/-5.8 ng x mmol creatinine(-1)) and LTE4 (58.5+/-5.3 versus 43.0+/-3.3 ng x mmol creatinine(-1)) were observed in the nonasthmatic subjects. There was also a small increase in urinary excretion of N(tau)-methylhistamine in the nonasthmatics, but not in the asthmatics. The increased urinary levels of 9alpha,11beta-prostaglandin F2 support mast cell activation with release of mediators following inhalation of mannitol. Increased bronchial responsiveness to the released mediators could explain the exclusive bronchoconstriction in asthmatic subjects.
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PMID:Evidence of mast cell activation and leukotriene release after mannitol inhalation. 1451 40

To study the role of mast cell activation in children with atopic eczema/dermatitis syndrome (AEDS), we measured levels of urinary 9alpha,11beta-prostaglandin F(2) (U-9alpha,11beta-PGF(2)) by enzyme-linked immunoassay in 88 children (mean age 44 months, range 3-135) with mild (n=32), moderate (n=34) or severe (n=22) AEDS, as well as in 72 non-atopic healthy controls. Fifty-eight of the children with AEDS were sensitized to common allergens (atopics) and 30 were not (non-atopics). Levels of U-9alpha,11beta-PGF(2) were higher in children with severe AEDS (median 324 microg/mmol creatinine, quartiles 220-593) than in controls (198, 102-389, p<0.001), whereas levels of U-9alpha,11beta-PGF(2) in moderate and mild disease were similar to controls. U-9alpha,11beta-PGF(2) levels were similar in atopic and non-atopic children, but in severe AEDS those with atopy had higher levels than those without atopy (p<0.05). The results suggest a role for mast cell activation in children with severe AEDS. Exacerbation of AEDS caused by allergen triggering may involve mast cell activation, and U-9alpha,11beta-PGF(2) may serve as a marker of this process.
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PMID:Urinary 9alpha,11beta-prostaglandin F(2) in children with atopic eczema/dermatitis syndrome: an indicator of mast cell activation? 1537 Jul 1

Aristolochic Acid Nephropathy (AAN) is regarded as a kind of toxic nephropathy caused by the formation of DNA- aristolochic acid adducts in renal parenchymal cells. However, the underlying mechanisms driving the progression of renal interstitial fibrosis in AAN still remains unclear. This study aims to elucidate the role of some immunological factors, especially mast cells (MCs), in the pathogenesis of AAN. Sixteen patients with AAN were enrolled in this study, including five acute and 11 chronic AAN. Monoclonal antibodies against human tryptase, alpha smooth muscle actin (alpha-SMA), and CD68 were applied on serial sections, which were further counterstained with Periodic Acid-Schiff. It was found that massive tryptase-positive MCs were observed in the fibrotic areas in chronic AAN, especially around thickened tubular basement membranes where myofibroblasts accumulated too. In contrast, MCs infiltrated to a less extent in acute AAN, and were barely found in normal control kidneys. In chronic AAN, the number of MCs in the tubulointerstitium was positively correlated with the degree of renal fibrosis (r=0.64, P <0.05), but not with serum creatinine levels. Meanwhile, the recruitment of MCs into the renal interstitium is accompanied with local proliferation of myofibroblasts. Macrophages were not abundant, neither in acute nor in chronic AAN. Our findings show for the first time that mast cell infiltration seems to be associated with the progression of fibrosis in the renal tubulointerstitium in chronic AAN.
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PMID:Mast cell infiltration associated with tubulointerstitial fibrosis in chronic Aristolochic Acid Nephropathy. 1585 Feb 77


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