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)

Human lung mast cells were obtained from pulmonary tissue of normal individuals and patients with chronic bronchitis or emphysema by enzymatic dispersion. Based on their density two mast cell subtypes, a formalin-sensitive (FS) and a formalin-insensitive (FI) cell type, could be separated. Although differences in anti-IgE-induced histamine release could be demonstrated for the mast cell subtypes of normal individuals, these experiments could not be performed for both mast cell subtypes from both patient groups. LTC4 and PGD2 release could be demonstrated for the FS- and FI-mast cell respectively. The release of PGD2 from FI-mast cells of patients with chronic bronchitis was enhanced as compared with normal subjects.
 ...
PMID:Mediator release from human lung mast cell subtypes in chronic bronchitis and emphysema. 247 45

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.
 ...
PMID:Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. 247 89

Glucocorticoids are potent anti-inflammatory drugs that are widely used in the treatment of allergic disorders. Their actions are often species specific or cell-type specific. Previous studies have demonstrated that glucocorticoids inhibit mediator release from mast cells derived from the peritoneum of mouse or rat and from guinea pig lung, but not those residing in human lung parenchymal tissue. In the present study, we have analyzed the effect of overnight culture with dexamethasone (10(-6) to 10(-7)M) on the subsequent IgE-dependent release of mediators from human mast cells derived from airway tissue, intestine, and skin. Airway tissue was passively sensitized with antigen-specific, IgE-rich serum during the culture period and subsequently challenged with ragweed antigen E. Skin and intestinal mast cells were challenged with anti-IgE. Histamine and immunoreactive LTC4 and PGD2 release was monitored in all experiments. Prostaglandin E release was quantitated in the experiments using airway tissue. Dexamethasone treatment failed to inhibit the release of mast cell mediators from all three tissues, but it inhibited the antigen-induced release of immunoreactive PGE from other cells residing in airway tissue. These results confirm earlier studies of the effects of glucocorticoids on human lung parenchymal mast cells, but contrast with the inhibitory effects of steroids observed in murine mast cells and human basophils.
 ...
PMID:Dexamethasone does not inhibit the release of mediators from human mast cells residing in airway, intestine, or skin. 247 59

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with anti-immunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with anti-immunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.
 ...
PMID:Mast cell heterogeneity in human lung tissue. 247 33

Mast cells and macrophages were isolated from human lung tissues by using density gradient centrifugation, cell sorter, and adherence techniques. Passively sensitized mast cells in the absence of exogenous arachidonic acid (AA) released leukotriene (LT)C4, LTD4, PGD2, and thromboxane-B2 when challenged with Ag, and in the presence of AA, released 5-hydroxyeicosatetraenoic acid (HETE) and 15-HETE in addition to the above metabolites. Passively sensitized macrophages did not release significant amounts of AA metabolites when challenged with Ag. However, these cells released LTB4, LTC4, LTD4, LTE4, 5-HETE, PGE2 and 6-keto-PGF1 alpha when co-incubated with activated mast cells. During co-incubation, mast cells also generated greater amount of AA metabolites than when they were activated alone. The stimulatory action of mast cells on macrophages was shown to be due to the extracellular factor(s) present in the supernatant of the activated mast cells. Both heat and trypsin inhibited the biologic activity of mast cell-derived stimulatory factor. In addition, extraction of mast cells' materials with chloroform or ether showed no activity associated with the organic phase, suggesting it possibly possesses a protein nature, such as peptides, protease, or peptidase. These results suggest that mast cell-macrophage interaction might be important in the generation of multiple mediators in the airways during immediate hypersensitivity reactions.
 ...
PMID:Mast cell mediators stimulate synthesis of arachidonic acid metabolites in macrophages. 249 26

Cells dispersed from human foreskin were passively sensitized with IgE and then depleted or enriched in mast cells by density gradient centrifugation. Arachidonic acid metabolism was initially studied by radio-high-performance liquid chromatography analysis of incubation media from cells that had been prelabeled with [3H] arachidonic acid. In subsequent experiments with unlabeled cells the eicosanoids were quantified by radioimmunoassay. Prostaglandin (PG)D2 was the major cyclooxygenase product released from purified mast cells challenged with anti-IgE or A23187. In density gradient studies there was a significant correlation between PGD2 and histamine release (r = 0.52, p less than 0.01) and between PGD2 release and the numbers of mast cells (r = 0.42, p less than 0.02). There was no correlation with the total numbers of nucleated cells. Other cyclooxygenase products were also detected, the formation of 6-keto-PGF1 alpha and PGE2 being principally associated with gradient fractions containing endothelial cells. Leukotriene (LT)C4 was the major lipoxygenase product detected, reaching a maximum of 3.87 +/- 0.56 ng/10(6) mast cells upon activation with anti-IgE compared with 35.37 +/- 7.22 ng/10(6) mast cells of PGD2. When normalized to histamine release and expressed in molar terms, skin mast cells released approximately 20-fold more PGD2 than LTC4. Thus, the cutaneous mast cell is one likely source of the PGD2 and LTC4 released during cutaneous immediate hypersensitivity reactions.
 ...
PMID:The IgE- and calcium-dependent release of eicosanoids and histamine from human purified cutaneous mast cells. 250 19

Human bronchial epithelial cells were isolated from macroscopically normal bronchi obtained from lobectomy specimens. Cells were grown in nutrient F12 medium, and after the third or fourth subculture they were stimulated with arachidonic acid, histamine, leukotrienes (LT) C4, D4, or E4, prostaglandin (PG) D2, anti-IgE, acetylcholine, bradykinin, or phorbol myristate acetate (PMA). Neither mast cell mediators (i.e., histamine, LTC4, LTD4, LTE4, or PGD2) nor anti-IgE stimulated the release of arachidonic acid metabolites from the epithelial cells. However, arachidonic acid, acetylcholine, bradykinin, and PMA stimulated the release of 15-hydroxyeicosatetraenoic acid (15-HETE) as major and prostaglandin E2 (PGE2) as minor products. The maximal release of 15-HETE and PGE2 occurred in 1 h with arachidonic acid stimulation and in 2 h with other stimuli. Arachidonic acid at 30 microM caused the release of 258 +/- 76 ng and 29 +/- 15 ng (n = 12) of 15-HETE and PGE2, respectively, from 10 x 10(6) epithelial cells, whereas acetylcholine, bradykinin, or PMA caused the release of approximately 2- to 10-fold less 15-HETE and PGE2. These results demonstrate that human bronchial epithelial cells selectively generate 15-HETE as the predominant arachidonic acid product and PGE2 as a minor metabolite. The role of bronchial epithelial cells and their mediators in the pathogenesis of bronchial hyperresponsiveness needs further study.
 ...
PMID:Release of 15-hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin E2 (PGE2) by cultured human bronchial epithelial cells. 251 53

The abundance of mast cells in human dermis, together with their ability to release a variety of vasoactive and pro-inflammatory mediators following cross-linkage of their cell-surface receptors for IgE, enables these cells to provide an effective defence mechanism within this organ. A similar defensive function is attributed to mast cells of other human organs such as intestine and lung which are in contact with the external environment and therefore susceptible to infiltration by foreign allergens and micro-organisms. However, mast cells of the skin apparently differ from those present in lung and intestine in being activated for histamine release by a variety of endogenous neuropeptides which stimulate the rapid release of histamine in the virtual absence of eicosanoids. This would provide a mechanism of neurogenic control of a variety of homeostatic functions such as blood flow, angiogenesis and fibroblast proliferation. Such processes would aid in the remodelling of tissue during wound healing, and increased numbers of mast cells have been noted around healing wounds of rat skin and areas of developing fibrosis. Neuropeptides modulate the activity of a variety of immuno-competent leucocytes including macrophages, monocytes and lymphocytes. The findings that skin mast cells are activated by neuropeptides suggest that these cells may also be included amongst those involved in neuro-immune interactions. Activation of skin mast cells by non-immunological stimuli may contribute to the aetiology of some forms of skin disease. Patients with chronic idiopathic urticaria appear to have enhanced vascular responsiveness to intradermal injections of the histamine liberator codeine suggesting that this disease may involve hyper-responsiveness of their mast cells to endogenous non-immunological stimuli. The findings of large increases in histamine accompanied by small increases in PGD2 in venous effluent of thermally challenged limbs of patients with cold- or heat-induced urticaria may suggest that their mast cells had been activated by a non-immunological stimulus. However, the interpretation of results gained using such relatively complex in-vivo systems are difficult, as the cellular origin of the detected mediators is by no means clear. However, it is hoped that in the future the alliance of newly developed in-vitro techniques to investigate mast cell function together with in-vivo methods to investigate their interaction with elements in their tissue environment will greatly increase our understanding of the role of the human skin mast cell in health and disease.
 ...
PMID:The human skin mast cell. 266 2

A diagrammatic representation of the interactions between mediators of hypersensitivity and leukocytes in early, late-phase, and ongoing asthma is shown in Figure 1. Early phase or immediate reactions are largely the result of bronchoconstriction consequent to the release of mediators such as histamine, PGD2, LTC4/D4, and PAF. The principal mediator cell (MC) is the mast cell (although other IgE receptor-bearing cells such as the macrophage, eosinophil, and platelet might also be involved in this immediate response). The stimulus for mediator cell activation may be either immunologic (IgE-dependent) or nonimmunologic (i.e., changes in osmolarity as a result of the respiratory water loss associated with exercise-induced asthma). Late-phase reactions appear to be a consequence of infiltration with neutrophils (N), eosinophils (E), and macrophages (M phi). These cells are recruited and activated either by mast cell-associated chemotactic factors [such as LTB4, PAF, the eosinophil chemotactic factor of anaphylaxis (ECF-A), or high-molecular weight neutrophil chemotactic activity (NCA (HMW))] and/or "lymphokines" derived from T-helper cells (TH) which have been stimulated by antigen processed by the antigen-processing cells (APC). These mononuclear cell interactions are under the control of regulatory T cells [T suppressor (TS) cells] and it is speculated that the availability of these subsets may determine the magnitude of the late-phase response. Lymphokines and monokines which selectively activate neutrophils, eosinophils, and monocytes include LIF, EAF, and IFN-gamma, respectively. Macrophage-derived tumor necrosis factor (TNF) also amplifies the inflammatory response by its capacity to enhance eosinophil cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inflammatory cells in bronchial asthma. 270 38

In this study, we have investigated the contribution of cholinergic-mediated bronchoconstriction in the airway response provoked by inhaled prostaglandin (PG)D2, its metabolite 9 alpha, 11 beta-PGF2, and PGF2 alpha, which are generated during mast cell activation in vivo and are potent bronchoconstrictor agonists in humans. The effect of prior inhalation of 1 mg ipratropium bromide (IB) on the bronchoconstrictor response to inhaled methacholine (MCh), PGD2, 9 alpha, 11 beta-PGF2, and PGF2 alpha was determined in 7 allergic asthmatic subjects by measuring changes in SGaw, FEV1, and Vmax30. Methacholine, PGD2, and 9 alpha, 11 beta-PGF2 caused concentration-related bronchoconstriction with PGD2 and 9 alpha, 11 beta-PGF2 being between 45 and 112 times more potent than MCh (p less than 0.05), depending on the method used to measure airway caliber. Preinhalation of IB displaced the concentration response curves to MCh between 69- and 196-fold to the right, and this was significantly greater than that observed with PGD2 (12- to 23-fold, p less than 0.02) and 9 alpha, 11 beta-PGF2 (12- to 22-fold, p less than 0.02). Ipratropium bromide inhibited the bronchoconstriction achieved with the highest concentration of agonist by 73 to 91% with MCh, 46 to 79% with PGD2, and 32 to 38% with 9 alpha, 11 beta-PGF2. Ipratropium bromide did not affect the bronchoconstriction pattern to inhaled PGF2 alpha, irrespective of the nature of the response. We conclude that although PGD2 and 9 alpha, 11 beta-PGF2 are potent contractile agonists of human smooth muscle in vitro, bronchoconstriction observed with these mediators in vivo results from a combination of both direct and cholinergic-mediated mechanisms.
 ...
PMID:Cholinergic-mediated bronchoconstriction induced by prostaglandin D2, its initial metabolite 9 alpha,11 beta-PGF2, and PGF2 alpha in asthma. 296 Feb 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>