The IgE- and calcium-dependent release of eicosanoids and histamine from human purified cutaneous mast cells.
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.
Robinson
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Immunopharmacology Group, Southampton General Hospital, U.K.
Benyon
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Holgate
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Church
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MK
D000906:Antibodies / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000494:pharmacology*; D015289:Leukotrienes / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D015230:Prostaglandin D2 / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors
D000906:Antibodies; D015289:Leukotrienes; D011453:Prostaglandins; D007073:Immunoglobulin E; D000001:Calcimycin; D006632:Histamine; D015230:Prostaglandin D2; D002118:Calcium