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 relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen-specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process.
J Immunol 1991 Dec 15
PMID:Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. 175 95

The extracellular form of 14-kDa group II phospholipase A2 has been found to accumulate at various types of inflammatory sites. In the present paper, we have studied the possible role of the extracellular 14-kDa group II phospholipase A2 in the process of prostaglandin production in activated rat mast cells. When mast cells obtained from the peritoneal cavity of rats were sensitized with IgE, challenged with antigen and then exposed to extracellular 14-kDa group II phospholipase A2, appreciable release of prostaglandin D2 was observed. Generation of prostaglandin D2 was dependent on the concentration of the phospholipase A2 as well as that of the antigen, while no appreciable prostaglandin D2 generation was observed with cells in the absence of the antigen. No histamine release was observed under the same conditions. Phosphatidylcholine in mast cell membranes was appreciably hydrolyzed to liberate free arachidonic acid when mast cells were incubated with 14-kDa group II phospholipase A2 added exogenously in the presence of the antigen. Both the generation of prostaglandin D2 and the release of arachidonic acid were retarded by inhibitors specific to 14-kDa group II phospholipase A2. Thus, 14-kDa group II phospholipase A2 may function in the process of inflammation by acting on IgE-antigen-primed mast cells, which are not fully activated, to generate eicosanoids.
FEBS Lett 1991 Dec 09
PMID:Eicosanoid generation from antigen-primed mast cells by extracellular mammalian 14-kDa group II phospholipase A2. 175 67

The inhibitory effect of various dipeptides on the neurotensin-degrading metallopeptidase, endopeptidase 24.16, was examined. These dipeptides mimick the Pro10-Tyr11 bond of neurotensin that is hydrolyzed by endopeptidase 24.16. Among a series of Pro-Xaa dipeptides, the most potent inhibitory effect was elicited by Pro-Ile (Ki approximately 90 microM) with Pro-Ile greater than Pro-Met greater than Pro-Phe. All the Xaa-Tyr dipeptides were unable to inhibit endopeptidase 24.16. The effect of Pro-Ile on several purified peptidases was assessed by means of fluorigenic assays and HPLC analysis. A 5 mM concentration of Pro-Ile does not inhibit endopeptidase 24.11, endopeptidase 24.15, angiotensin-converting enzyme, proline endopeptidase, trypsin, leucine aminopeptidase, pyroglutamyl aminopeptidase I and carboxypeptidase B. The only enzyme that was affected by Pro-Ile was carboxypeptidase A, although it was with a 50-fold lower potency (Ki approximately 5 mM) than for endopeptidase 24.16. By means of fluorimetric substrates with a series of hydrolysing activities, we demonstrate that Pro-Ile can be used as a specific inhibitor of endopeptidase 24.16, even in a complex mixture of peptidase activities such as found in whole rat brain homogenate.
Eur J Biochem 1991 Dec 05
PMID:Specific inhibition of endopeptidase 24.16 by dipeptides. 176 Oct 32

The structure of rat carboxypeptidase A2 (CPA2), which has a unique specificity for tryptophan-containing COOH-terminal peptides, has been determined in an unliganded state at 1.9-A resolution and refined to a crystallographic R-factor of 18.3%. Comparison of the structure of CPA2 with that of bovine carboxypeptidase A (referred to here as CPA1) reveals that the specificity of the former for larger amino acids probably arises from two amino acid replacements within the binding cavity (Thr268----Ala and Leu203----Met), coupled with differences in the positions of conserved residues in a surface loop on one face of the specificity pocket. The position of the reactive-site surface loop may be affected also by a disulfide bridge between Cys210 and Cys244. In this unliganded form of the enzyme, Tyr248 takes up a position interior to the specificity pocket and is distinct from that observed in bovine CPA1. The structural differences between CPA1 and CPA2 correlate strongly with crystallographically determined temperature factors and thus appear to be largest where the enzyme is flexible.
J Biol Chem 1991 Dec 25
PMID:Structural evolution of an enzyme specificity. The structure of rat carboxypeptidase A2 at 1.9-A resolution. 176 58

Differential nasal responsiveness to environmental tobacco smoke (ETS) has been documented in humans and we hypothesized that this reflects differential responsiveness to c-fiber stimulation. We compared the response to intranasal capsaicin in subjects with and without a history of ETS-rhinitis. We challenged 10 ETS-sensitive and 11 ETS-nonsensitive subjects intranasally with 25 mg of lactose powder followed by 25 pg to 25 ng of capsaicin in 25 mg of lactose. Subjects rated nasal symptoms and underwent nasal lavage. In each lavage, the concentrations of albumin (an index of vascular permeability), kinins and histamine (a marker of mast cell activation) were measured. Nasal lavage tosyl-L-arginine methyl ester (TAME)-esterase activity, which can be a reflection of mast cell activation, increased vascular permeability or glandular secretion, was also determined. Subjects with a history of ETS-rhinitis reported more rhinorrhea than subjects without a history of ETS-rhinitis (P less than .01). No significant increase occurred in nasal lavage histamine, albumin or kinins in either subject group. TAME-esterase activity (presumably a reflection of increased glandular secretion) increased greater than 1000 cpm in 12/21 subjects (designated "TAME-producers"), but this was unrelated to ETS-sensitivity. TAME producers showed a dose-dependent increase in TAME-esterase activity, whereas TAME nonproducers showed no change at any capsaicin dose. We conclude that capsaicin causes nasal symptoms and glandular stimulation without evidence of increased vascular permeability or mast cell activation. ETS-rhinorrhea symptoms in humans appear related to c-fiber stimulation. The absence of c-fiber-induced glandular secretion, although not related to ETS-sensitivity, was associated with decreased sneezing and increased symptoms of capsaicin-induced nasal burning.
J Pharmacol Exp Ther 1991 Dec
PMID:Effect of intranasal capsaicin on symptoms and mediator release. 176 79

The regulation of the plasma membrane potential of rat peritoneal mast cells at the resting state and during activation was investigated using bisoxonol as a potential-sensitive fluorescent dye. Fluorescence microphotography showed that this negatively charged probe was not only present in the plasma membrane, but was also distributed in the cytoplasm. The intracellular localization of bisoxonol was confirmed by conducting experiments which showed that bisoxonol fluorescence was not enhanced in ATP-permeabilized mast cells. Rotenone (10(-7) M) and oligomycin (10(-6) M) did not change the fluorescence of bisoxonol showing, therefore, mitochondrial depolarization was not recorded with bisoxonol and suggesting that bisoxonol may represent a useful probe to study plasma membrane potential changes in the absence of exocytosis. We showed that, in non-stimulated mast cells, the blockade of the sodium pump enhanced the fluorescence of bisoxonol as did gramicidin a non selective ionophore used to fully depolarize the cells. High concentration of potassium (30 mM) as well as different ionic channel blockers did not significantly change the fluorescence intensity of bisoxonol, suggesting that ionic channel permeabilities were not involved in maintaining the resting plasma membrane potential of mast cells. Mast cells stimulated by compound 48/80 completely lost the fluorescence, shown by fluorescence microphotography, suggesting that exocytotic phenomena might induce a dye redistribution which is not only due to changes in the plasma membrane potential. In mast cells pretreated with pertussis toxin, which blocks mast cell-exocytosis, compound 48/80 induced a delayed (2 min) decrease of bisoxonol fluorescence which was shown to be dependent on the activity of the sodium pump. Considering that bisoxonol is a useful potential-sensitive probe in exocytosis-deprived mast cells, our results suggest that the sodium pump is mainly involved in the changes of plasma membrane potential of mast cells.
Biochim Biophys Acta 1991 Dec 09
PMID:The use of the potential-sensitive fluorescent probe bisoxonol in mast cells. 176 50

1. To test the hypothesis that the in vivo inhibition of angiotensin converting enzyme in a patient who presents atopy, results in a significant increase in cutaneous bradykinin and prostaglandin production, the effect of enalapril on the cutaneous hypersensitivity reaction was examined in 10 atopic volunteers. 2. A crossover study design was used and volunteers were randomly allocated to treatment with either enalapril (10 mg) alone, or in combination with indomethacin (75 mg), with and without ketotifen (1 mg). Drugs were administered twice daily for 2 days. 3. Allergen (Southern Grass Mix) was administered intradermally 2 h after last drug dosage and the surface areas of the immediate wheal-and-flare-reactions were measured 15 min later. The late phase of the cutaneous response was evaluated 6 h later by determining skinfold thickness and surface area. 4. Enalapril alone had no effect on any of the parameters measured. 5. The cutaneous hypersensitivity reaction was significantly reduced with regard to both immediate and late cutaneous responses when the indomethacin and ketotifen combination was added to enalapril therapy. 6. When only indomethacin was added to enalapril pretreatment the flare reaction was significantly reduced, but whealing was unaffected. 7. This study presents further evidence that mast cell mediators other than prostaglandins are involved in the cutaneous hypersensitivity reaction. Furthermore, that endogenous bradykinin production after enalapril pretreatment either never reaches the supraphysiological concentrations used in previous experiments, or that bradykinin is rapidly and effectively broken down to inactive peptides by other carboxypeptidase enzymes.
Br J Clin Pharmacol 1991 Dec
PMID:Effect of enalapril on allergen-induced cutaneous hypersensitivity reaction. 176 63

The lesions of nine patients with early striae distensae (SD) during puberty were examined by light and electron microscopy. Specific changes were seen in very early stage SD, and in clinically uninvolved skin 0.5 to 3 cm remote from the edge of the long axis of the SD lesions. Sequential changes of elastolysis accompanied by mast cell degranulation appeared first, followed by an influx of activated macrophages that enveloped fragmented elastic fibers. The relationships among elastic fibers, mast cells, and macrophages seen in the present work suggest their critical roles in the process of SD formation, especially in the early stage. Our results also indicate that the elastic fiber is the primary target of the pathological process, and the abnormalities extend as far as 3 cm beyond the lesion into normal skin.
J Cutan Pathol 1991 Dec
PMID:Mast cell degranulation and elastolysis in the early stage of striae distensae. 177 50

This study was designed to examine the possible role of sex steroid hormones on mast cells localized in uterus draining lymph nodes (UDLN) in mice. Young virgin estrous animals had more mast cells than diestrous animals in both the UDLN and popliteal lymph nodes (PLN). In retired breeders there were no differences in mast cell numbers of estrous and diestrous animals. There were no differences in mast cell numbers among weanling and older animals in diestrous in the UDLN but, in the PLN, mature animals in either diestrous or estrous had more mast cells than the PLN of weanlings. In mature animals, ovariectomy did not alter mast cell number in either node. However, ovariectomy of weanlings increased mast cell numbers in the PLN but not in the UDLN. These results suggest that the UDLN behaves as a nonclassical target organ for the endocrine system, with mast cell number variations related to gonadal steroid levels.
Brain Behav Immun 1991 Dec
PMID:Mast cells in female mouse lymph nodes. 177 32

The ultrastructure of mast cells from the nine normal inferior turbinates were compared with those found in eight patients with perennial allergic rhinitis due to house dust mite allergy. Forty-six mast cells from normal patients were found in forty blocks and eighty cells were found in thirty-three blocks in patients with perennial allergy suggesting an increase of mast cell numbers in perennial allergy. There were no basophils outside the blood vessels and whole mast cells were found only in the submucosa. There was no difference in the morphology of cells of different sizes. Mast cells were more degranulated in the allergic mucosa. Degranulation, irrespective of cell size was found at all depths of the mucosa. A review of the literature covered the in vivo and in vitro descriptions of the ultrastructural morphology of human mast cells in the respiratory tract.
J Laryngol Otol 1991 Dec
PMID:Ultrastructure of nasal mast cells in normal subjects and patients with perennial allergic rhinitis. 178 51


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