title: The IgE- and calcium-dependent release of eicosanoids and histamine from human purified cutaneous mast cells.
abstract: 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.
authors.affiliation: Immunopharmacology Group, Southampton General Hospital, U.K.
authors.forename: C
authors.initials: C
authors.lastname: Robinson
authors.forename: C
authors.initials: C
authors.lastname: Benyon
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: M K
authors.initials: MK
authors.lastname: Church
mesh_terms: 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
chemical_list: D000906:Antibodies; D015289:Leukotrienes; D011453:Prostaglandins; D007073:Immunoglobulin E; D000001:Calcimycin; D006632:Histamine; D015230:Prostaglandin D2; D002118:Calcium