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Biomedical subjects

M A Bray

Publications and source records attributed to M A Bray.

At least 55 records · Page 3Linked to original sources
PubMed1980

Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes.

Arachidonic acid is metabolised either by cyclooxygenases to produce prostaglandins and thromboxanes or by lipoxygenases to produce mono-, di- and trihydroxyeicosatetraenoic acids (HETEs). Polymorphonuclear leukocytes (PMNs) release HETEs, including mono- and dihydroxy fatty acids, when exposed to stimuli such as the calcium ionophore A23187 (refs 1, 2). The mono-HETEs are assumed to be of particular importance with respect to effects on leukocyte function because they have been shown to possess both chemotactic and chemokinetic activities towards PMNs and eosinophils. However, we have now shown that the chemokinetic and aggregating activities released from rat and human PMNs exposed to ionophore A23187 (ref. 5) are not due to the release of mono-HETEs but to that of 5, 12-di-HETE (leukotriene B). This compound is active over the concentration range 10 pg ml-1 to 5 ng ml-1.

Animals↗
PubMed1980

Lipoxygenase products and the polymorphonuclear leucocyte.

Polymorphonuclear leucocytes (PMNs), when exposed to the calcium ionophore A23178, release into the supernatant a substance that causes the aggregation and chemokinesis of fresh PMN suspensions. Release of these activities is inhibited by preincubation with drugs known to inhibit lipoxygenase pathways of arachidonic acid metabolism but is unaffected by cyclooxygenase inhibitors. The substance responsible for these activities has been identified as leukotriene B and this compound has been shown to be a potent chemokinetic and aggregatory agent for PMNs over the range 10 pg to 5 ng ml-1.

Arachidonic Acids↗
PubMed1980

Calcium ionophore A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leucocytes.

1. Rat and human polymorphonuclear leucocytes (PMNs) when exposed to calcium ionophore A23187 10 microM release products which cause aggregation of rat PMNs and chemokinesis of human PMNs. 2. Aggregating and chemokinetic activities are rapidly generated; maximal release occurs after 4 min, and can be detected in dilutions of the supernatant of up to 1:1000. 3. Generation of aggregating and chemokinetic activities is inhibited by nordihydroguaiaretic acid 10(-4) to 10(0-7) M, 5,8,11,14-eicosatetraynoic acid 10(-4) and 10(-5) M, BW 755C 10(-4) M and benoxaprofen 10(-4) M, all compounds known to inhibit lipoxygenase pathways of arachidonic acid (AA) metabolism. 4. Conventional non-steroidal anti-inflammatory agents, such as aspirin and indomethacin, inhibited little or not at all the generation of these activities. 5. We conclude that the aggregating and chemokinetic activities induced by A23187 represent generation of biologically active products of lipoxygenase pathways of AA metabolism.

Anti-Bacterial Agents↗
PubMed1980

Time-lapse cinematography of the capillary tube cell migration inhibition test.

The kinetics of human and guinea pig cell migration inhibition have been studied using time-lapse cinematography of cells migrating from capillary tubes. Guinea pig and human cells exhibit markedly different kinetics in the absence of inhibitors. Specific antigen causes a dose-related inhibition of migration for up to 60 h using guinea pig cells and a peak of inhibition after 18 h using the human leucocyte system. The timing of measurement of maximum activity more critical for the latter test. The kinetics of lymphokine generation have been examined and the migration inhibitory activity of the plant mitogen (PHA), a Kurloff cell product and a continuous cell line supernatant have been compared with the inhibitory profiles of lymphokine preparations and specific antigen.

Animals↗
PubMed1979

Inhibition of human lymphocyte transformation as an in vitro parallel line bioassay for anti-human lymphocyte globulin.

Horse anti-human lymphocyte globulin (HALG) is now widely clinically, but the variable immunosuppressive potency of different preparations of HALG has necessitated development of an accurate, reproducible in vitro assay of HALG potency. Currently available tests have several disadvantages, as well as showing little correlation with in vivo activity of the preparations tested. Incorporation of tritiated thymidine into lymphocytes, stimulated with mitogen (PHA) or antigen (PPD) and the inhibition of this process by HALG is described. ID50S and potency ratios have been determined for four HALG preparations. The ID50S obtained with these preparations were reproducible and the potency ratios obtained using 3 + 3 parallel line bioassay were similarly reproducible, a change in rank order being observed only once in ten assays. These in vitro results correlate with in vivo skin graft data. It is suggested that this technique could be used for evaluation of HALG preparations on peripheral blood from potential recipients.

Animals↗
PubMed1979

Prostaglandin and thromboxane production by human and guinea-pig macrophages and leucocytes.

The ability of partially purified human and guinea-pig haematogenous cell populations, when cultured in vitro, to metabolise arachidonic acid (AA) has been studied. Supernatants from 24 hour cell culture have been subjected to analysis for products of AA metabolism by gas chromatography with electron-capture detection. The cell types studied were human peripheral blood monocytes (both glass adherent and non-adherent), neutrophils, eosinophils and leukemia leucocytes; thoracic duct lymphocytes and lung alveolar macrophages. From the guinea-pig, induced and non-induced macrophage or neutrophil enriched peritoneal exudate populations, lymph node cells, peritoneal eosinophils and peripheral blood platelets were examined. Supernatants were assayed for the presence of PGE2, PGD2, PGF2 alpha, TXB2 and 6-keto-PGF1 alpha. In all types studied PGE2 and TXB2 were the major products formed. The identification of PGE2 and TXB2 was confirmed by GC/MS with multiple ion monitoring. The results have been compared with other reports and their possible significance discussed in relation to the proposed role of prostaglandins as mediators and modulators in immunopathology.

Animals↗
PubMed1978

Anti-inflammatory drug actions on allergic responses in guinea-pig skin.

Five non-steroidal anti-inflammatory drugs (indomethacin, naproxen, meclofenamic acid, feprazone and phenylbutazone: NSAIDs) and three glucocorticosteroids (dexamethasone, hydrocortisone and prednisolone) have been tested as local inhibitors of increased vascular permeability in guinea-pig skin. Lesions were induced by histamine or by antigen to evoke type I (passive cutaneous anaphylaxis), type III (reverse passive Arthus) and type IV (delayed hypersensitivity) allergic reactions. NSAIDs and glucocorticosteroids caused either weak, inconsistent inhibition or slight, high-dose inhibition of the response to histamine. None of the drugs tested showed significant inhibition of the type IV response. The NSAIDs caused dose-related inhibition of both type I and type III responses whereas glucocorticosteroids were ineffective. Maximum inhibition with the NSAIDs was never greater than 50--60% Feprazone, meclofenamic acid and indomethacin were the most potent inhibitors of histamine, PCA and Arthus responses respectively. The possible significance of the effects of these anti-inflammatory agents on vascular permeability is discussed.

Animals↗
PubMed1978

Prostaglandins as regulators in cellular immunity.

Guinea-pig peritoneal macrophages have been shown to generate substantial concentrations of E-type prostaglandins during culture in vitro. Partially purified lymphokine preparations stimulate PGE production by macrophages. Exogenous PGE1 and PGE2 are potent inhibitors of lymphocyte activation and secretion of lymphokines causing lymphocyte mitogenesis and macrophage migration inhibition. Also indomethacin augments the secretion of these lymphokines in vitro. It is therefore suggested that production of PGE by macrophages provides a physiological mechanism for the regulation of lymphocyte activation in reactions of delayed hypersensitivity.

Animals↗
PubMed1978

Prostaglandin production by macrophages and the effect of anti-inflammatory drugs.

1 Macrophages derived from peritoneal cavity inflammatory exudates of guinea-pigs produced substantial amounts of prostaglandin E2-like activity during in vitro culture, so providing the basis for an experimental model of prostaglandin production during inflammatory reactions. 2 Dose-related inhibition of prostaglandin biosynthesis was demonstrated by 16 acidic non-steroidal anti-inflammatory drugs. 3 Seven anti-inflammatory glucocorticosteroid preparations inhibited prostaglandin production in a dose-related manner. The relative potencies of dexamethasone, prednisolone and hydrocortisone were consistent with clinical anti-inflammatory ranking. Cortisone, however, failed to inhibit macrophage prostaglandin production. 4 Three other agents used in the treatment of inflammatory joint diseases were examined. Sodium aurothiomalate inhibited prostaglandin production, although higher concentrations were toxic to macrophages. D-Penicillamine did not affect macrophage prostaglandin production. Colchicine, in contrast, enhanced prostaglandin production at some concentrations. 5 The probable significance of macrophages as a source of prostaglandins, during inflammatory responses, is discussed.

Animals↗
PubMed1978

Prostaglandins and inflammatory cell movement in vitro.

The prostaglandins PGE1, E2, F2alpha, and A1, had no significant cell migration inhibitory or chemotactic activity for guinea pig peritoneal exudate cells when tested in vitro using respectively the capillary tube cell migration test and the Boyden chamber test for chemotaxis. PGE1 and PGE2 also did not affect the positive chemotactic action of lymphokine. The proposed role of prostaglandins as chemotactic agents in inflammatory responses therefore should be treated with some caution.

Animals↗