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 postulate that fibrocystic changes in the female breast are the end result of a series of biochemical events initiated by the mast cell degranulation products histamine and heparin. Two mechanisms are proposed which could lead to mast cell degranulation in breast tissue. First, low progesterone levels lead to decreased intracellular cAMP levels in mast cells which enhance mast cell degranulation. Second, low progesterone levels lead to increased solubilization of breast collagen during tissue turnover. Susceptible individuals may undergo an allergic reaction to soluble collagen resulting in further mast cell degranulation. The degranulation products histamine and heparin may stimulate increased stromal proliferation and vascularization respectively. We provide evidence for the occurrence of histamine release by demonstrating an increased incidence of allergic symptoms in white women with fibrocystic breast changes.
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PMID:Allergic etiology of benign fibrocystic changes of the breast. 244 63

In allergic and nonallergic lung diseases, if intraluminal mast cells adhere to airway epithelium, inflammatory mediators released from activated mast cells may reach high local concentrations and thus greatly affect airway function. To determine whether mast cells adhere to airway epithelial cells, radiolabeled or unlabeled dog mastocytoma cells were incubated with cultured dog tracheal epithelial cells, with extracellular matrix substrates, and with cryostat-cut sections of dog trachea. Mast cells adhered well to cultured epithelial cells (35 +/- 13% adhesion, mean +/- 1 SD, n = 23) but adhered poorly to types I and IV collagen or to fibronectin (less than 7.5% mean adhesion in all cases). Similarly, in tracheal tissue sections, mast cells adhered preferentially to epithelial cells in surface epithelium or in submucosal glands but not to basal membrane or connective tissue. Adhesion to cultured epithelial cells was a characteristics of a subpopulation of mast cells, could persist for more than 48 h, did not require energy or the presence of divalent cations, and was not mediated by a known family of leukocyte-associated adhesion glycoproteins. Adhesion was completely abolished by pretreatment of mast cells with pronase E or proteinase K but not with trypsin (up to 10 micrograms/ml at 37 degrees C for 20 min each). In contrast, pretreatment of cultured epithelial cells with any of these proteinases had no effect on adhesion. It is concluded that dog mastocytoma mast cells adhere to dog tracheal epithelial cells and do so selectively. It is suggested that mast cell adhesion to airway epithelium may play a role in the effectiveness of mast cell-epithelial cell interactions, and thus, in certain lung diseases, airway function may be affected by intraluminal mast cells more than is currently appreciated.
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PMID:Selective adhesion of mast cells to tracheal epithelial cells in vitro. 245 Sep 14

The functional role of mast cells in rheumatoid synovium was investigated by assessing the ability of mast cell tryptase to activate latent collagenase derived from rheumatoid synoviocytes. Tryptase, a mast cell neutral protease, was demonstrated in situ to reside in rheumatoid synovial mast cells, by an immunoperoxidase technique using a mouse mAb against tryptase, and in vitro to be released by dispersed synovial mast cells after both immunologic and nonimmunologic challenge. Each rheumatoid synovial mast cell contains an average of 6.2 pg of immunoreactive tryptase and the percent release values of this protease correlated with those of histamine (r = 0.58, p less than 0.01). The ability of purified tryptase to promote collagenolysis was demonstrated in a dose-dependent fashion using latent collagenase derived from rheumatoid synovium, synovial fluid, IL-1-stimulated cultured synoviocytes, and partially purified latent collagenase derived from conditioned media, with between 10 and 92% of the collagen substrate degraded. [3H] Collagen, treated with tryptase-activated latent collagenase, was subjected to electrophoresis on SDS polyacrylamide gels and autoradiography showed the collagen degradation pattern (A, B) characteristically produced by collagenase. Mast cell lysates also activated synovial latent collagenase yielding 24% digestion of collagen substrate. This activator in mast cell lysates could be inhibited by diisopropylflurophosphate or by immunoadsorption of tryptase. Thus, mast cells may activate metalloproteinases and play a role in the catabolism of collagen that occurs in rheumatoid synovium.
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PMID:Activation of latent rheumatoid synovial collagenase by human mast cell tryptase. 245 61

Serine proteases in mast cell granules, such as chymase, atypical chymase, and tryptase, which are major proteins in the granules, may play important roles in the process of immunoglobulin E (IgE)-mediated degranulation and in pathobiological alterations in tissues. Indeed, inhibitors of chymase, substrate analogs, and antichymase F(ab')2, but not inhibitors of tryptase, markedly inhibited histamine release induced by IgE-receptor bridging but not that induced by Ca ionophore. In contrast, inhibitors of metalloprotease inhibited histamine release induced not only by IgE-receptor bridging but also by Ca ionophore. These results suggest that chymase and metalloprotease are involved at different steps in the process of degranulation. The extents of inhibition of histamine release were closely correlated with the amounts of the inhibitors of chymase accumulated in the granules. After degranulation, the released proteases may in part contribute to pathobiological alterations in allergic disorders through generations of C3a anaphylatoxin and thrombin by human and rat tryptase, respectively, and those of angiotensin II and a chemotactic factor of neutrophils by human and rat chymase, respectively. Moreover, chymase and atypical chymase from rat were shown to destroy type IV collagen, and human tryptase was found to hydrolyze various plasma proteins, such as fibrinogen and high-molecular-weight kininogen. The biological activities of tryptase and chymase from rat may be regulated by their dissociation from and association with trypstatin, an endogenous inhibitor of these proteases.
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PMID:Biological functions of serine proteases in mast cells in allergic inflammation. 246 15

The porphyrias are the only group of diseases caused by endogenous phototoxic agents. While patients with erythropoietic protoporphyria and those with porphyria cutanea tarda both have skin lesions on sun-exposed areas, there are differences in their cutaneous manifestations. Based on information discussed in this chapter, the following pathophysiologic mechanisms can be proposed. In porphyria cutanea tarda, photoactivation of the complement system in the presence of uroporphyrin results in activation of dermal mast cells, which release their proteases. This results in dermal-epidermal separation, reflected clinically as skin fragility and vesicles. The interaction between activated mast cells with fibroblasts, the nature of which is still unclear, may contribute to fibrosis and sclerodermoid skin changes. The stimulatory effect of uroporphyrin on collagen biosynthesis by fibroblasts, which occurs independent of irradiation, may be responsible for the sclerodermoid lesions seen at sun-exposed as well as sun-protected areas. In erythropoietic protoporphyria, mast cell activation can occur as the result of complement activation induced by protoporphyrin and irradiation. Protoporphyrin and irradiation may also directly induce the release of preformed and generated mediators from mast cells, a process mediated at least in part by peroxidation. The release of mast cell mediators may account for the erythema, edema, and urticaria observed in patients with erythropoietic protoporphyria upon exposure to sunlight. Interaction of mast cells with fibroblasts, and the direct membrane-damaging effect of protoporphyrin and irradiation on the latter, may contribute to the waxy thickening of skin seen in chronically sun-exposed areas of these patients. There are, however, many unanswered questions. What accounts for the different biological effects of mast cell-derived mediators: dermal-epidermal separation in one, erythema and urticaria in the other? The fragmentation of dermal collagen bundles associated with cleavage beneath the lamina densa, and the hyperpigmentation and hypertrichosis observed in some patients with porphyria cutanea tarda remain unexplained. What is the mechanism of the reduplication of blood vessel basal lamina in the non-sun-exposed areas of both types of patient? Are there any roles for cytokines and epidermal cell-derived eicosanoids? While it is clear that the pathogenesis of cutaneous lesions in porphyria cutanea tarda and erythropoietic protoporphyria involves interactions among inflammatory mediators and various cells in skin, much still needs to be done to further our understanding of their pathophysiology.
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PMID:Mechanisms of phototoxicity in porphyria cutanea tarda and erythropoietic protoporphyria. 248 74

For many years, the mast cell has been considered the principal cell in bronchial asthma. However, there is some evidence to suggest that platelets might be involved in asthma. One of this evidence is the induction by platelet-activating factor or airway hyperreactivity and its inhibition by disodium cromoglycate and ketotifen. Since platelet aggregation is an index of platelet activation, we investigated the effect of these drugs on platelet aggregation induced by ADP, collagen and arachidonate in human platelet-rich plasma. The results obtained show that both drugs inhibit the effect of ADP and collagen. Ketotifen was also shown to inhibit the aggregation induced by arachidonate. The mechanism of the antiasthmatic action of these drugs is at present not clear. If platelet activation as it has been proposed, is involved in asthma, the antiaggregant effect of ketotifen and cromoglycate might be part of its beneficial effect in the treatment of asthma.
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PMID:Effect of ketotifen and disodium cromoglycate on human platelet aggregation. 250 3

Neurofibromas contain fibroblasts and many mast cells, and recent hypotheses have linked fibrous tissue growth to activated mast cells. We describe the ultrastructure of mast cells and fibroblasts in a case of neurofibromatosis. Mast cells were numerous and showed extensive signs of activation. Mast cells were often intimately associated with fibroblasts, and mast cell granules could be seen inside fibroblasts ('transgranulation'). The fibroblasts were also activated. These results suggest that interactions between mast cells and fibroblasts may be important in the prominent collagen production that takes place in these tumors.
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PMID:Ultrastructural evidence for mast cell activation in a case of neurofibromatosis. 251 21

The histology of 17 cases of basal cell carcinoma and dermis next to the carcinoma was observed. The results showed that the mast cell number was markedly increased in the dermis near the basal cell carcinoma. There was an increase in the collagen fibers between the carcinoma and dermis tissues, forming a thin membrane around the carcinoma tissue. These findings suggest that the carcinoma-associated antigen may activate the lymphocytes to produce certain lymphokine which stimulates the proliferation and differentiation of the mast cell precursors. Histamine and other active mediators released from mast cells stimulate fibroblasts to synthesize collagen fibers which form a thin membrane between the carcinoma and dermis. The membrane plays a protective role against tumor dissemination.
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PMID:[Basal cell carcinoma and mast cells]. 263 34

The conditions and cell sources for colony stimulating activity (CSA) production by nasal polyp epithelial scrapings were examined. Epithelial scrapings removed from patients were grown to confluence during 7 days as monolayers of epithelial cells in media supplemented with fetal calf serum (FCS) on collagen-coated microwell plates. Growth kinetics of nasal polyp epithelial cells (NPECs) were determined, and CSA in NPEC conditioned medium (CM) was assessed with density-gradient separated, nonadherent peripheral blood mononuclear cells in standard 14-day methylcellulose assays. Nasal polyp cultures in the presence of 5% or 15% FCS (vol/vol) demonstrated significantly more epithelial cell proliferation than cultures at 0% and 1% FCS. There were comparable metachromatic cell counts in polyp epithelial scrappings from allergic and nonallergic donors. Similarly, NPEC CM from allergic and nonallergic donors had equivalent CSA for basophil/mast cell (BMC) and eosinophil (EO) lineages, respectively. CSA production was enhanced under conditions of higher FCS concentration and NPEC proliferation. These studies confirm an epithelial cell origin of BMC and EO growth and differentiation factors derived from nasal polyps and point to the existence of a unique microenvironment for BMC and EO development provided by polyp epithelium that appears to be independent of the presence of an allergic diathesis.
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PMID:Hematopoietic growth factor production by cultured cells of human nasal polyp epithelial scrapings: kinetics, cell source, and relationship to clinical status. 265 45

Bronchial asthma is an inflammatory disease. The characteristic pathological features of epithelial cell loss, goblet cell hyperplasia, increased deposition of collagen beneath the basement membrane, mast cell degranulation, and inflammatory cell infiltration of the mucosa are not limited to fatal asthma. Similar inflammatory events have been observed in subjects who would be considered to have clinically stable asthma. These observations would suggest that pharmacological treatment directed against the underlying inflammatory processes in asthma should not be limited to those patients with severe forms of the disease.
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PMID:Inflammatory processes in bronchial asthma. 266 40


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