Platelet-activating factor in bronchoalveolar lavage fluid from asthmatic subjects.

Bronchoalveolar lavage (BAL) was performed on 28 asthma patients, 7 patients with emphysema and 11 control subjects. Total and differential cell counts were performed and cellular metabolic activity was assessed using luminol and lucigenin amplified chemiluminescence. BAL supernatants were assayed for platelet-activating factor (PAF) and lyso-PAF using a sensitive guinea-pig bioassay. Eight of the asthma patients but none of the emphysema patients or control subjects had PAF in their BAL fluid. Lyso-PAF was measurable in BAL fluid in most subjects and no differences were detected between groups. Among the asthma patients, the presence of PAF in BAL supernatant was significantly associated with a combination of low neutrophil and high lymphocyte counts (p less than 0.05) and with macrophage metabolic activity as assessed by lucigenin chemiluminescence (p less than 0.05).

Actions of prostaglandin E2 metabolites on skin microcirculation.

The actions of prostaglandin, E2 on skin microcirculation were compared with two of its metabolites. 2-10 ng prostaglandin E2, 2-10 micrograms 15-keto prostaglandin E2 and 5-10 micrograms 13,14-dihydro-15-keto prostaglandin E2 produced the following dose-related effects: increased area and intensity of erythema in human skin, increased vascular permeability in rat skin, potentiation of the increased vascular permeability elicited by either histamine or bradykinin, potentiation of carrageenan-induced oedema in the rat paw. The prostaglandin E2 metabolites are about 1000 times less active than the parent prostaglandin and are unlikely to account for the inflammatory actions of prostaglandin E2.

Factors affecting prostaglandin synthesis by rat skin microsomes.

Prostaglandin synthesis by rat skin was measured by a radiochemical method and the adrenochrome spectrophotometric method. About 70% of the total enzyme activity was located in the microsomal fraction. Incubation with (1-14C) arachidonic acid resulted in the formation of prostaglandins F2alpha, E2 and D2. The biosynthesis of these 3 prostaglandins was stimulated by reduced glutathione and hydroquinone, and was markedly dependent on pH. A number of non-steroid anti-inflammatory drugs produced a dose related inhibition of prostaglandin biosynthesis. Five potent corticosteroid anti-inflammatory agents previously found to be inhibitory when a skin homogenate was used did not inhibit prostaglandin synthesis by the microsomal fraction.

Inflammatory effects of prostaglandin D2 in rat and human skin.

1 Intradermal injection of prostaglandin (PG) D1 and D2 in the human forearm produced a long-lasting dose-related erythema. When compared with prostaglandin E1 or E2 the order of potency for erythema production was PGE1 greater than PGE2 greater than PGD2 greater than PGD1. 2 In rat skin, prostaglandin D2 but not D1 caused an increase in vascular permeability as quantitated by the Evans blue method and the 125I-albumin extravasation technique. Prostaglandin E2 was 3-5 times more potent than prostaglandin D2. 3 Prostaglandin D2 (10 ng) potentiated the increase in vascular permeability in rat skin produced by histamine, but not that produced by bradykinin. 4 Prostaglandin D2 (10, 20 and 50 ng) did not elicit oedema or hyperalgesia in the rat paw oedema test, but potentiated carrageenan-induced oedema; hyperalgesia was potentiated by doses of 100 ng and above.