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)

Rat peritoneal mast cells (RPMC) exposed to protoporphyrin (PP) and incandescent light (IL) become refractory to the stimulatory effects of compound 48/80. Once initiated, this refractory state continues to develop even after removal of the light source and is essentially complete within 30 min. While this state of unresponsiveness appears to be relatively permanent in the dark, prolonged incubation in the light (greater than 80 min) induces cell lysis. We have shown that the resistant state is not specific for the mast cell stimulator compound 48/80. Mast cells passively sensitized with IgE and illuminated for 30 min in the presence of 100 ng/ml PP also fail to release histamine upon stimulation by anti-rat IgE, anti-rat F(ab')2, concanavalin-A (Con-A), and the calcium ionophore A23187. The inability to respond to immunological stimuli could not be ascribed to the reversible loss of membrane-bound IgE from its receptor. While the binding of either the inducer to IgE or IgE to its receptor may actually be impaired in refractory cells, the significance of such impairments on the development of the resistant state in these cells is precluded by the inability of A23187 to either increase intracellular 45Ca2+ levels or induce histamine release. The data suggest that the RPMC refractory state develops as a result of covalent inter- and/or intramolecular cross-linking of membrane proteins. Furthermore, this cross-linking may involve sulfhydryl or amino groups essential to either stimulus transduction, or the histamine secretory process itself.
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PMID:Inhibition of rat peritoneal mast cell histamine secretion by protoporphyrin and incandescent light. 257 37

Introduction of a reactive monohaptenic chemical into the sensitized organism will not normally result in elicitation of immediate reactions. Rather, the first products of chemical conjugation to suitable carriers in vivo are monohaptenic, conjugates which are inhibitory according to the bridging concept, stating that the initiating event for mast cell and basophil activation is a cross-linking of membrane-bound antibody by dihaptenic or oligohaptenic antigen. Simple calculations and quantitative data are presented to show that built-in inhibition is indeed a powerful barrier to any rapidly occurring allergenic manifestation which depends on the formation of divalent conjugates. If and when such a reaction does nevertheless occur, special requirements have to be invoked. One possibility is that the chemical or drug as such, i.e. without conjugation to a carrier, is an elicitor of anaphylaxis. Such compounds are known in a guinea pig passive cutaneous anaphylaxis model system, but there is evidence that they may also play a role in clinical situations. These monovalent elicitors possess in addition to the haptenic moiety an auxiliary group. The auxiliary group requirements were studied in the guinea pig passive cutaneous anaphylaxis system by using synthetic peptides with an N-terminal 2-carboxy-4,6-dinitrophenyl group as the hapten and phenylalanine and modified phenylalanine at the C-terminus as auxiliary group. The conclusions are that effective auxiliary function depends on the benzene ring and neighboring carboxyl groups in selected positions. Anaphylactogenicity is high when the haptenic and auxiliary groups can act independently, i.e. when separated by a peptide chain of considerable length. Potent anaphylactogens with close linkage of the two groups have, however, also been found. It is unlikely that the passive cutaneous anaphylaxis elicitations observed here are mediated by some form of indirect bridging of membrane-bound antibody.
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PMID:Immediate hypersensitivity to drugs and simple chemicals: the efficacy of monovalent elicitors. 257 65

Secretory cells undergoing release and recovery events related to constitutive and/or stimulus-initiated secretion might be expected to undergo distinctive changes in morphology as well. We studied the release and recovery events of human mast cell secretion stimulated by antibody to immunoglobulin E. We used enzymatically digested mast cells from human lung specimens further purified by countercurrent centrifugation elutriation. Release kinetics were like those reported for isolated human lung mast cells. In two complete kinetic experiments we restudied these early release patterns (0 to 30 minutes). Mast cells, either stimulated or controls, were then cultured and sampled for electronmicroscopic studies at periodic intervals (3 to 48 hours). We describe events of the late recovery period here, although some overlap with processes seen in early recovery samples occurred. Mast cells that released nearly all their cytoplasmic granules and exteriorized the containers, eg, granule-channel membranes, underwent progressive enlargement of Golgi structures and development of numerous small cytoplasmic vesicles and small, membrane-bound granules filled with particulate and dense content. Ultimately, new mature cytoplasmic granules of all substructural patterns occurred. Nuclear blast changes and expansion of cytoplasmic mass accompanied this period of new granule synthesis. Mixed recovery patterns were present in individual cells. These represented the morphological expression of a variety of recovery events. Thus, some cells showed a combination of channel recovery and remodeling to form new granule containers within which condensation of content produced crystalline patterns, as well as synthesis of new granules, as described here. This morphological versatility resulted in multiple mast cell morphological phenotypes during these release and recovery processes.
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PMID:Human mast cells synthesize new granules during recovery from degranulation. In vitro studies with mast cells purified from human lungs. 325 49

The murine mast cell line PB-3c is dependent on interleukin 3 (IL-3) with respect to survival and proliferation. These cells also require IL-3 to display antigen-mediated serotonin release, which is coupled to a transient increase of cytosolic free calcium ([Ca2+]i). The antigen-mediated exocytosis is inhibited by phorbol 12-tetradecanoate 13-acetate (PTA), an activator of phospholipid/Ca2+-sensitive protein kinase. In contrast, the malignant mast cell variant PB-1 is IL-3 independent with respect to proliferation but is unable to undergo antigen-mediated exocytosis. Yet this cell line exhibits basal levels of [Ca2+]i, serotonin content, and numbers of IgE receptors comparable to those of PB-3c cells. Subcellular distribution studies revealed that the specific activity of cytosolic protein kinase C of PB-1 cells was only 40% of that found in PB-3c cells. Furthermore, the PB-1 cells showed a significantly higher specific activity of membrane-bound protein kinase C than PB-3c cells. Scatchard plot analysis of [3H]-phorbol 12,13-dibutyrate binding to intact PB-1 cells demonstrated the presence of 20% high-affinity (Kd = 6 nM) and 80% low-affinity (Kd = 60 nM) phorbol ester receptors, whereas PB-3c cells displayed only the low-affinity phorbol ester binding. Immunological characterization of protein kinase C from both cell lines revealed the presence of a normal 77-kDa protein kinase C holoenzyme in both cell lines. In addition, a 72-kDa protein kinase C-related protein band was found mainly in the membrane fraction of the PB-1 variant. It is suggested that this altered and membrane-bound form of protein kinase C may be involved in the blockage of the antigen-mediated exocytosis of PB-1 cells.
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PMID:Altered protein kinase C in a mast cell variant defective in exocytosis. 349 90

The mode of interaction of human hemoglobin (Hb) with the red cell membrane was investigated with special reference to the effect on oxygen binding properties and Hb-membrane binding constants. Compared to free native Hb, the membrane-bound native Hb showed a strikingly lowered oxygen affinity and smaller response to organic phosphates such as 2,3-diphosphoglycerate and inositol hexaphosphate. Similar effects of membrane binding were also observed for intermediately cooperative Hbs such as N-ethylmaleimide-treated Hb (NES-Hb) and iodoacetamide-treated Hb (AA-Hb), but very small effects were observed for non-cooperative Hb, i.e., carboxypeptidase A-treated Hb (des-His-Tyr Hb). The magnitude of the affinity lowering was in the order: NES-Hb greater than native Hb greater than AA-Hb much greater than des-His-Tyr Hb. In the presence of inositol hexaphosphate, the three chemically modified Hbs showed an increased oxygen affinity when bound to the red cell membrane, probably due to partial replacement of bound inositol hexaphosphate by membrane. The binding to membrane caused a slight decrease in cooperativity for native Hb, but no distinct change in cooperativity was observed for the three modified Hbs. These results imply: a) the red cell membrane binds to deoxyHb more strongly than to oxyHb; b) the difference in membrane binding affinity between oxyHb and deoxyHb is closely related to the quaternary structure change in the Hb molecule occurring upon oxygenation. The higher affinity of the membrane for deoxyHb than for oxyHb apparently disagrees with the conclusion drawn by earlier investigators. However, the present binding experiments by means of ultrafiltration proved that the red cell membrane actually binds to deoxyHb much more strongly than to oxyHb, validating the present conclusion based on oxygenation experiments. Our results are consistent with those obtained recently by other investigators using a synthetic peptide or the cytoplasmic fragment of red cell membrane band 3.
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PMID:The binding of hemoglobin to red cell membrane lowers its oxygen affinity. 359 47

The distribution and ultrastructure of mast cells in the duck were studied. Carnoy's fluid was found to be the best fixative, and Padawer's method was found to be useful in demonstrating the metachromasia. Mast cells were seen in many of the organs and were most numerous in the proventriculus. Perivascular location was frequently seen. The ultrastructure resembled that of the chicken mast cell. The cell contained different types of membrane-bound granules, some of which were electron-dense and mottled.
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PMID:Distribution and ultrastructure of mast cells in the duck. 381 2

The ultrastructure of globule leukocytes is described in the nasal and tracheal respiratory epithelium of three boys suffering from chronic airway infections. The globule leukocytes lie free in the intercellular spaces and appear to be migratory cells. They are characterized by intracytoplasmic membrane-bound globules, variable in number, size, shape, and internal structure. The globules may apparently release their content between the neighboring epithelial cells. Human globule leukocytes are also characterized by the presence of intracytoplasmic rod-shaped bodies, the significance of which is not known. They usually display an extended juxta-nuclear Golgi apparatus, presumably involved in the formation of the globules. Comparison of the fine structure of the globules in the globule leukocytes with that of the granules found in the subepithelial mast cells does not support a mast cell origin for human globule leukocytes. On morphological grounds, natural killer cells are postulated as a possible source for globule leukocytes. The function of globule leukocytes is briefly discussed. We presume that the globule leukocytes belong to the group of migrating and secreting cells involved in the defense of the organism against foreign material.
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PMID:Globule leukocytes in the respiratory epithelium of human upper airways: an ultrastructural study. 384 37

Calcium permeability of basophil and mast cell membranes is stimulated on allergen binding to its specific membrane-bound IgE. This entry of Ca2+ ions into the cell triggers the degranulation and secretion process. Disodium cromoglycate (cromolyn DSCG), the disodium salt of 1,3-bis(-2-carboxychromon-5-yloxy)-2-hydroxypropane, inhibits the degranulation and release of anaphylactic mediators, and has found wide application in the treatment of allergic bronchial asthma. Accumulated evidence indicates that this inhibition takes place by blocking the calcium uptake. To localize its site of action, the drug has been covalently conjugated to fluorescent polyacrylamide and polyglutaraldehyde beads (0.7 and 0.2 microns in diameter, respectively). We show here that these drug-bead conjugates (DBC) do prevent the drug penetrating into the cell without reducing its ability to inhibit histamine release (Table 1). Furthermore, we show a specific Ca2+-dependent binding of the DBC to the membranes of rat peritoneal mast cells (RPMC) and basophils.
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PMID:A binding site on mast cells and basophils for the anti-allergic drug cromolyn. 615 90

Regeneration of rat mast cells was studied by TEM from 10 s to 48 h after secretion of histamine induced by compound 48/80. During the first 2 h, small intracellular cavities, formed during compound exocytosis and containing non-membrane-bound remnants of the granules, tended to coalesce, and after 2 h of incubation regeneration started. After 6 h, all the cavities had fused into one large central cavity which contained the remnants of the granules and remained open to the exterior during the entire period. The plasma membrane microfolds which disappeared just after secretion were reformed during regeneration. They were apparently involved in endocytotic-like activity and coated vesicles also appeared beneath the plasmalemma (membrane recycling?). The fate of the granule remnants in the cavity is unknown, as regeneration was not completed after 48 h which is the longest survival time obtained so far in ultrastructural studies of mast cell regeneration in vitro.
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PMID:Electron microscopic study of the regeneration in vitro of rat peritoneal mast cells after histamine secretion. 616 80

Mast cells secrete histamine, glycosaminoglycans, arachidonic acid derivatives, enzymes, and possibly whole granules. Physiologic stimuli include the bridging of membrane-bound IgE molecules by antigen, the anaphylatoxins C5a and C3a, and the neurotransmitter acetylcholine. Evidence is presented that a 'spontaneous' histamine release may be of biological significance. While the actual trigger of this process is unknown, it appears to be regulated by the concentration of histamine in the environment. It is suggested that the spontaneous release is responsible for maintaining a certain histamine concentration in the body fluids. After mast cell stimulation by IgE cross-linking or drugs changes in lipid metabolism, an influx of Ca2+ ions into the cell and fusions of the perigranular and the cytoplasmic membranes are observed. The physiologic role of the mast cell and its mediators is still a mystery.
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PMID:Triggering of mast cells. 618 14


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