Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review demonstrates that basophils reflect skin and lung mast cell reactivity and show characteristic changes in mediator release associated with clinical disease. Although the numbers of IgE molecules and IgE receptors on basophils have been enumerated, these have, in most instances, little influence on the release of histamine after challenge. There is, rather, a parameter of "releasability" that may be a major variable in allergic disease states. Basophils contain and release histamine, the eosinophil chemotactic factor of anaphylaxis (ECFA), a slow reacting substance of anaphylaxis (SRS-A), and a kallikrein. The release process is controlled by hormone-basophil receptor interactions that determine the cyclic AMP level; plasma and tissue adenosine levels appear prominent in this control. Histamine feeds back to negatively modulate basophil and mast cell release through a specific histamine 2-receptor; it also inhibits lymphocyte and neutrophil function. Like neutrophils, basophils contain beta-glucuronidase while neutrophils contain SRS-A and a low-molecular-weight ECF. The stimuli for primary basophil and neutrophil release are, however, quite different, although phagocytic stimuli, which fail to cause basophil mediator release, potentiate the IgE response. It is concluded that basophols play a significant in vivo role in inflammation by acting as an interface between foreign antigens, the serum cascade systems, and other inflammatory cells.
 ...
PMID:The role of basophils in inflammatory reactions. 7 20

The reactive-site sequence of a proteinase inhibitor can be written as . . . -P3-P2-P1-P'1-P'2-P'3- . . . , where-P1-P'1-denotes the reactive site. Three semisynthetic homologues have been synthesized of the bovine trypsin-kallikrein inhibitor (Kunitz) with either arginine, phenylalanine or tryptophan in place of the reactive-site residue P1, lysine-15. These homologues correspond to gene products after mutation of the lysine 15 DNA codon to an arginine, phenylalanine or tryptophan DNA codon. Starting from native (virgin) inhibitor, reactive-site hydrolyzed, still active (modified) inhibitor was prepared by chemical and enzymic reactions. Modified inhibitor was then converted into inactive des-Lys15-inhibitor by reaction with carboxypeptidase B. Inactive des-Lys15-inhibitor was reactivated by enzymic replacement of the P1 residue according to Leary and Laskowski, Jr. The introduction of arginine was catalyzed by an inverse reaction with carboxypeptidase B, while phenylalanine or tryptophan were replaced by carboxypeptidase A. The reactivated semisynthetic inhibitors were trapped by complex formation with either trypsin or chymotrypsin. The enzyme - inhibitor complexes were subjected to kinetic-control dissociation, and the semisynthetic virgin inhibitors were isolated. The inhibitory properties of the semisynthetic inhibitors have been investigated against bovine trypsin and chymotrypsin and against porcine pancreatic kallikrein and plasmin. The homologues with either lysine or arginine in the P1 position are equally good inhibitors of trypsin, plasmin and kallikrein. The Arg-15-homologue is a slightly more effective kallikrein inhibitor than the Lys15-inhibitor. The semisynthetic phenylalanine and tryptophan homologues, however, are weak inhibitors of trypsin and still weaker inhibitors of kallikrein, but are excellent inhibitors of chymotrypsin. Their association constant with chymotrypsin is at least ten times higher than that of native Lys-15-inhibitor. A dramatic specificity change is observed with the phenylalanine and tryptophan homologues, which in contrast to the native inhibitor do not at all inhibit porcine plasmin. Thus, the nature of the P1 residue strongly influences the primary inhibitory specificity of the bovine inhibitor (Kunitz).
 ...
PMID:Replacement of lysine by arginine, phenylalanine and tryptophan in the reactive site of the bovine trypsin-kallikrein inhibitor (Kunitz) and change of the inhibitory properties. 12 27

1. All the porcine pancreas enzymes tested, regardless of their pI's were adsorbed on Amberlite CG-50 (a weakly acidic cation exchange resin) at pH 4, where the ion-exchange group (carboxyl group) is not dissociated. The adsorption is hardly influenced by ionic strength. 2. At pH 4, the adsorbed enzymes were partially eluted by organic solvents such as 50% propanol. 3. The adsorbed enzymes were effectively eluted by increasing the pH from 4 to 6. Trypsin (pI 10.5) was eluted before carboxypeptidase A (pI 4.5 AND 5.3) WITH 0.5 M acetate buffer, whereas the former enzyme was eluted after the latter enzyme with 0.2 M 3,3-dimethyl glutarate buffer. However, with either buffer, the elution order of enzymes was not always the same as the order of the pI's. 4. By a single Amberlite CG-50 column chromatography of porcine pancreas extracts, kallikrein, carboxypeptidase B, deoxyribonuclease, carboxypeptidase A, and trypsin were purified 100-fold, 16-fmately 13%. The purification procedures included treatment with protamine, ammonium sulfate fractionation, treatment with acid, DE-32 cellulose column chromatography, gel filtration on Sephadex G-100, preparative polyacrylamide gel electrophoresis, and affinity chromatography on 5' AMP-Sepharose 4B. The last procedure, affinity chromatography on 5' AMP-Sepharose 4B, was useful for the removal of other dehydrogenases. The enzyme which was homogeneous, as shown by polyacrylamide gel electrophoresis, had a molecular weight of about 92,000. The optimum pH was at 10.0 and isoelectric point at 5.2. The enzyme accepted both L-fucose and D-arabinose as substrate, but was specific for NAD+ as coenzyme. Km values were 0.15 mM, 1.4 mM, and 0.07 mM for L-fucose, D-arabinose, and NAD+, respectively. A single enzyme catalyzed the oxidation of L-fucose and D-arabinose, which had the same configurations of hydroxyl groups from C-2 to C-4. The reaction products obtained with L-fucose as substrate were L-fucono-lactone and L-fuconic acid. The L-fucono-lactone was an immediate product of oxidation and was hydrolyzed to L-fuconic acid spontaneously. This reaction was irreversible. Therefore, it is likely that L-fucose dehydrogenase is involved in the initial step of the catabolic pathway of L-fucose in rabbit liver.
 ...
PMID:Hydrophobic-ionic chromatography. Its application to purification of porcine pancreas enzymes. 31 32

Using the indirect immunofluorescence technique, the basic kallikrein-trypsin inhibitor of bovine organs, Trasylol, could be localized in tissue mast cells of bovine lung, liver, pancreas and parotid gland. Identification of cells exhibiting specific fluorescence as tissue mast cells was achieved by combined light and electron microscopic diagnosis of bovine liver tissue sections. The presence of Trasylol in mast cells explains the widespread distribution of this inhibitor in functionally totally different organs or tissues of the bovine organism, as determined earlier by biochemical means. Identification of Trasylol as a mast cell constituent will facilitate the search for the biological function of this inhibitory protein in connection with a unique and highly specialized cell population.
 ...
PMID:Immunofluorescence studies indicate that the basic trypsin-kallikrein-inhibitor of bovine organs (Trasylol) originates from mast cells. 37 18

Pulmonary edema and plasma kininogen consumption caused by intravenously administered adrenaline, were inhibited in rats pretreated with acetylsalicylic acid, but not in rats pretreated with indomethacin or sodium salicylate. The possibility of a connection between this edema and mast cell-linked activation of kallikrein by adrenaline is discussed, as well as the possible role of acetylsalicylic acid acting as an acetylating inhibitor of these processes.
 ...
PMID:Acute pulmonary edema and plasma kininogen consumption in the adrenaline-treated rat: inhibition by acetylsalicylic acid and resistance to salicylate and indomethacin. 116 Oct 51

Axon reflex vasodilation following injury to the skin of the pinna of the ear was studied in rats by a thermometric method. Post-traumatic vaso-dilatation did not occur in animals treated with tyrosine ethyl ester, an inhibitor of chymotrypsin. Vasodilatation was not affected by treatment of the rats with chlorpheniramine (antihistamine) or cyproheptadine (antihistamine and anti-serotinin) or with aprotinin, soybean trypsin inhibitor, epsilon-aminocaproic acid or tosyl arginine methyl ester (inhibitors of trypsin and of some other proteinases). Taken in conjunction with the results of other investigations, these findings indicate that in the skin of the rat: (a) histamine and serotinin are not essential for the initiation of axon reflexes, and (b) the chymotrypsin-like proteinase of mast cell granules, released as the result of antidromic activity in sensory axons, may act as a kininogenase and be responsible for causing dilatation of arterioles at the efferent limb of the axon reflex.
 ...
PMID:Evidence for the involvement of vasoactive constitutents of mast cells in axon reflex vasodilatation in the skin of the rat. 125 6

Staphylococcal enterotoxin B (SEB) was tested in rodent mast cell cultures for the release of serotonin. Both rat RBL-2H3 mast cells and murine peritoneal cells released serotonin after SEB stimulation in culture. Release of serotonin in RBL-2H3 cells depended on the concentration of SEB; an appreciable release was seen at 50 micrograms/ml. The release of serotonin was not due to cell death. Serotonin release could be enhanced by bradykinin but not by vasoactive intestinal peptide, substance P, lipopolysaccharide from Salmonella typhimurium, the calcium ionophore A23187, acetylcholine, adenosine, 5-hydroxyeicosatetraenoic acid, indomethacin, or phorbol myristate acetate. SEB bound directly to the membrane of RBL-2H3 mast cells, and the SEB-binding site, the presumptive receptor, appeared to be a protein. The SEB receptor could not be capped under membrane-capping conditions, and serotonin release could not be enhanced by attempts to cross-link the receptor. These results suggest that mast cells may be an important cell type involved in SEB toxicosis and that release of serotonin may be enhanced by activation of the kinin-kallikrein system.
 ...
PMID:Effects of staphylococcal enterotoxin B on rodent mast cells. 137 85

The prerequisite for rational therapy of male fertility disorders is an exact diagnosis. While the possibilities of influencing disturbances of spermiogenesis are limited, male adnexal diseases can be successfully treated in many cases. Drugs for the treatment of fertility disorders must be applied with this in mind, and empiric therapy is often performed in addition to causal treatment which, however, may be quite rationally determined. The therapeutic spectrum in andrology includes antibiotic and antiphlogistic agents, mast cell blockers, zinc, vitamins, and immunosuppressive drugs (corticosteroids). These agents are used for the treatment of inflammatory diseases of the testes and the accessory glands or for suppression of antispermatozoal antibodies. Hormonal disturbances are infrequently encountered by the andrologist, but they can be treated, with proven efficacy, with gonadotrophins, gonadotrophin-releasing hormone (GnRH) or androgens. In certain cases that are not hormonally related, the use of antiestrogens (clomifene, tamoxifen) as stimulating agents may be successful. Furthermore, tissue hormone releasing proteases (kallikrein) can be used both therapeutically (especially in motility disturbances that are not due to structural flagellar defects) and diagnostically (in order to distinguish between inflammatory and noninflammatory testicular damage). Anticholinergics and alpha-sympathomimetics are applied to ameliorate ejaculation or emission failure. In addition to a review of these treatment forms, the development of new concepts, e.g. angiotensin converting enzyme (ACE) inhibitors, is discussed.
 ...
PMID:Guidelines for drug treatment of male infertility. 170 88

Allergic rhinitis is a classic example of a type I immunological reaction. After allergic provocation tests a biphasic reaction is seen in the respiratory tract that is more pronounced in the lower than in the upper respiratory tract due to the physiological changes during the nasal cycle. The early phase of the immediate reaction starts some minutes after allergen provocation. After 5-10 h the nasal symptoms (discharge, blockage, sneezing and itching of the nose) reappear, a phenomenon which is called the "late-phase response" (LPR). The LPR is of great clinical importance in the pathophysiology of perennial allergic rhinitis and phenomena such as nasal priming and nasal hyper-reactivity. The most important effector cell of the early phase of the immediate reaction is the mast cell, whereas basophils, eosinophils and neutrophil granulocytes seem to be more important for the LPR. There is also evidence for morphological and functional heterogeneity of mast cells in man. The role of the chemotactically immigrated eosinophils in allergic reactions has not been clear until now: the eosinophil-derived mediators may enhance or inhibit the allergic reaction. Also the eosinophils show different morphological and functional states (so-called hypo- and hyperdense eosinophils). The symptoms of allergic rhinitis (sneezing, discharge, blockage, itching of the nose) are caused by different mediators, of which the most important is histamine. Other mediators or modulators of the allergic reactions are leucotrienes, prostaglandins, PAF, serotonin, and the kallikrein-kinine and complement systems. In recent years many regulatory peptides have been detected in the human nasal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Current pathophysiologic aspects of allergic rhinitis. I]. 226 46

Certain manifestations of the allergic response, such as vasodilation and edema, may be attributed to the involvement of kinins, but, as yet, little data exist to show how these peptides could be produced during IgE-mediated events. We now report that purified human lung mast cells contain a kininogenase that is released in a dose-dependent fashion by anti-IgE. Release of kinin-generating activity parallels that of histamine and, like histamine release, kininogenase release is temperature-dependent. Kininogenase release also parallels increasing histamine release when mast cells of increasing size are stimulated with an optimal level of anti-IgE. Finally, when mast cells of greater than 99% purity were optimally challenged, kininogenase activity again paralleled histamine levels in the release supernatant and residual cell pellet. The mast cell kininogenase appears to be a preformed mediator in that it occurs in lysates of unstimulated mast cells of greater than 99% purity. Optimal generation of kinin from highly purified human low molecular weight kininogen occurred at pH 5.5 and in 8 preparations was 380 +/- 237 ng kinin/h/10(6) mast cells (means +/- SD). Thus, human lung mast cells contain a kininogenase that is released during, and may participate in, IgE-mediated inflammatory disorders in humans.
 ...
PMID:Immunoglobulin E-mediated release of a kininogenase from purified human lung mast cells. 241 Nov 78


1 2 3 4 Next >>