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)

We investigated the release of the 5-lipoxygenase derivatives of arachidonic acid (AA) in purified human basophils and compared them with similar results obtained in the human lung mast cell. We have shown that purified basophils (average purity = 51 +/- 6%) challenged with 0.1 microgram/ml anti-IgE released histamine (35 +/- 9%), and LTC4 (32 +/- 10 ng/10(6) cells) but failed to release measurable quantities of immunoreactive LTB4. In contrast, the non-specific stimulus, A23187, caused the release of histamine and both LTC4 (279 +/- 95 ng/10(6) cells) and LTB4 (148 +/- 41 ng/10(6) cells). Closer analysis of the data revealed an inverse relationship between the levels of LTB4 released and the purity of the basophils, strongly suggesting that the contaminating monocytes were responsible for LTB4 synthesis. Purified human lung mast cells have been shown to release 6 ng of immunoreactive LTB4/10(6) cells, indicating that basophils release significantly less LTB4 following an IgE-mediated challenge. In a series of experiments using highly purified basophils prelabeled with [3H]AA, we demonstrated that exposure to 0.1 microgram/ml anti-IgE led to the release of [3H]LTC4, with no detectable [3H]LTB4, whereas exposure to 1.0 micrograms/ml A23187 caused the release of [3H]LTC4 and smaller quantities of [3H]LTB4, [3H]LTD4, and [3H]LTE4. We failed to detect any [3H]LTB4 in the cell pellet following challenge with either anti-IgE or A23187, indicating that LTB4 was not synthesized and retained within the cell pellet. Finally, we found that exogenously added [3H]LTB4 was not metabolized, either by basophils alone or by basophils stimulated with anti-IgE (0.1 microgram/ml).
 ...
PMID:Purified human basophils do not generate LTB4. 244 28

The effect of antigen (ovalbumin) challenge on smooth muscle contraction and release of sulfidopeptide leukotrienes and histamine from superfused, actively sensitized guinea pig trachea was examined. Maximum concentrations of ovalbumin caused the release of 16 +/- 4 ng/g immunoreactive sulfidopeptide leukotriene (i-LT) and 27 +/- 3% of the endogenous histamine (x +/- S.E.M., n = 19). High performance liquid chromatography combined with a sulfidopeptide leukotriene radioimmunoassay was used to demonstrate that on a molar basis, approximately 10% of the leukotriene immunoreactivity recovered was LTC4, 45% LTD4 and 45% LTE4. Indomethacin slightly increased ovalbumin-induced histamine release and substantially enhanced (3-fold) i-LT release from the trachea. Neither the profile nor rate of sulfidopeptide leukotriene release was altered by indomethacin. Indomethacin had no effect on the maximum amplitude of the antigen-induced contraction but significantly enhanced the magnitude of contraction observed after 10 min of antigen exposure. These results demonstrate that actively sensitized airways synthesize and release sulfidopeptide leukotrienes upon challenge with specific antigen and that endogenously formed LTC4 is efficiently metabolized to LTD4 and LTE4. The results with indomethacin support the hypothesis that indomethacin potentiates antigen-induced airway contraction in vitro by enhancing the release of mast cell associated mediators.
 ...
PMID:Antigen-induced sulfidopeptide leukotriene release from the guinea pig superfused trachea. 244 85

The clinical features of systemic mastocytosis have been ascribed to mast cell-dependent mediators, but there have been no studies of their release from isolated cells. We have investigated the release of histamine and eicosanoids from isolated spleen cells obtained from tissue of a mastocytosis patient undergoing therapeutic splenectomy. Dispersed cell preparations contained lymphocytes 65.9%, monocytes/macrophages 22.3%, neutrophils 9.9%, mast cells 1.1%, and eosinophils 0.8%; upon challenge with 0.1-3.0 microM A23187 they released histamine much greater than PGD2 greater than TXB2 greater than LTB4 greater than LTC4 approximately equal to LTD4 greater than LTE4. With immunological activation of passively sensitized cells, histamine and PGD2 release had similar dose-response characteristics, but TXB2, LTC4, LTD4, and LTE4 release differed in reaching maximum at 50 micrograms/ml and declining at 125 micrograms/ml anti-human IgE. Percoll centrifugation separated most of the histamine-containing cells to the middle of the gradient, but they were refractory to release with 0.3 microM A23187 or 50 micrograms/ml anti-IgE. Spontaneous release of histamine from these cells was not abnormally high (1.3%-4.5%). Electron microscopy of tissue sections revealed large numbers of mast cells with empty granules. It is possible that the refractory cells observed are such mast cells where intracellular histamine is no longer granule-associated. Most net histamine and PGD2 release was confined to cells at the bottom of the gradients (1.078-1.09 g/ml), although some release of PGD2 occurred near the top (1.05-1.058 g/ml). There was a significant correlation between the net release of histamine and PGD2 with both immunological (r = 0.92; n = 16) and A23187 (r = 0.97, n = 14) activation. These studies provide evidence for a link between PGD2 and histamine release in mastocytosis spleen cells.
 ...
PMID:The immunoglobulin E- and calcium-dependent release of histamine and eicosanoids from human dispersed mastocytosis spleen cells. 245 Jan 44

Mast cells of human skin, but not lung, adenoids, tonsils, or intestine, release histamine in response to substance P, vasoactive intestinal polypeptide, and somatostatin. The substance P receptor of skin mast cells is not of the NK-1, NK-2 or NK-3 subtypes of smooth muscle. Time course and calcium dependency of release by peptides differed from anti-IgE. With anti-IgE, the molar ratios of histamine:PGD2:LTC4 generated by skin mast cells was 1,000:25:2, whereas with substance P these ratios were 1,000:1:0.1. Similar results were obtained with the other neuropeptides. The ability of peptides to stimulate skin mast cell histamine release suggests a mechanism whereby their release from dermal nerve endings is coupled to changes in microvasculature.
 ...
PMID:Interaction of neuropeptides with human mast cells. 246 22

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

Pretreatment of rat peritoneal mast cells with either Staurosporine or an analog K-252a, lead to a dose-related inhibition of histamine release when stimulated with Anti-IgE (IC50: Staurosporine = 110 nM; K-252a = 100 nM). In contrast, the two PKC inhibitors (1-1000 nM) failed to inhibit histamine release induced by compound 48/80 (0.5-1 micrograms/ml). Exposure of Anti-Asc-IgE sensitized mouse bone marrow derived mast cells to Asc-BSA lead to the release of both histamine (510 ng +/- 12.6 ng/10(6) cells) and immunoreactive Leukotriene C4 (27.0 +/- 12.6 ng/10(6) cells). LTC4 release was inhibited by Staurosporine and K-252a with an IC50 of 75 nM for both compounds. Pretreatment of rat peritoneal mast cells with PMA 100 nM lead to a small but significant release of histamine (18.3 +/- 3.6%). Pretreatment of these cells with K-252a or Staurosporine lead to a dose related inhibition of histamine release with an ED50 of 10 nM for Staurosporine and 60 nM for K-252a. Treatment of rat peritoneal mast cells with the calcium ionophore A23187 lead to a significant release of histamine which was not inhibited by either of the two kinase inhibitors (0.1-1000 nM). The two kinase inhibitors also inhibited mouse bone marrow derived mast cell proliferation in response to IL-3 with IC50 of 80 nM for Staurosporine and 270 nM for K-252a.
 ...
PMID:Differentiation of second messenger systems in mast cell activation. 247 99

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


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