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Biomedical subjects

F M Cunningham

Publications and source records attributed to F M Cunningham.

At least 73 records · Page 4Linked to original sources
PubMed1986

Psoriatic skin lesions contain biologically active amounts of an interleukin 1-like compound.

The presence of neutrophil chemoattractant material in aqueous extracts of lesional psoriatic scale has been investigated by use of an agarose microdroplet chemokinesis method in combination with ultrafiltration and high-performance liquid chromatography (HPLC). Fractions were also assayed for murine thymocyte co-stimulating activity. Aqueous extracts of psoriatic scale contained significantly greater neutrophil chemokinetic activity than extracts of scale from normal skin. Successive ultrafiltration of extracts showed that the chemokinetic material was 10 to 30 kd. Heat lability and gel filtration HPLC characteristics suggested that the major chemokinetically active material in aqueous extracts of psoriatic scale is different from C5a des arg. Reversed-phase HPLC of 0.1% trifluoroacetic acid/acetonitrile extracts of psoriatic scale revealed two clearly resolved peaks of chemokinetic activity, the major peak consistently containing thymocyte co-stimulating activity. No significant neutrophil chemokinetic activity was seen in fractions after reversed-phase HPLC of scale from normal skin. These findings suggest that a major portion of the neutrophil chemoattractant activity in aqueous extracts of psoriatic scale is due to interleukin 1-like material, which may play a role in the pathogenesis of this disease.

Adult↗
PubMed1986

The chemokinetic response of psoriatic and normal polymorphonuclear leukocytes to arachidonic acid lipoxygenase products.

Polymorphonuclear leukocytes (PMN) from ten patients with chronic stable plaque psoriasis, five of whom had more than 40% skin involvement and five with less than 20% involvement, responded in a dose-related fashion to stimulation with the arachidonic acid lipoxygenase products 5- and 12-hydroxyeicosatetraenoic acid (5- and 12-HETE) and leukotriene B4 (LTB4) in an in vitro chemokinesis assay. There was no significant difference in either the random migration or the chemokinetic response of psoriatic PMN to LTB4 when compared to the responses of PMN from a group of age- and sex-matched healthy controls. Psoriatic PMN migrated further in response to low doses of 5- and 12-HETE although the distance moved after maximal stimulation was no different to that observed in controls. No significant difference was observed in the responses of PMN obtained from patients with less than 20% skin involvement when compared to those with more extensive psoriasis. The small differences measured between the chemokinetic responses of psoriatic and control PMN to the lipoxygenase products tested are unlikely to be of pathogenetic significance.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1986

Topical steroid treatment reduces arachidonic acid and leukotriene B4 in lesional skin of psoriasis.

Topical clobetasol propionate or vehicle ointment was applied daily for 3 days to psoriatic plaques on eight patients. Skin chamber exudates from untreated, steroid and vehicle treated lesions were assayed for arachidonic acid (AA), leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) before, and at 24 h and 72 h after treatment. Significant reductions in AA and LTB4 were observed at 72 h in steroid treated lesions. The reduction in 12-HETE levels observed after steroid treatment was not statistically significant. PGE2 levels in lesional psoriatic skin were unaltered. The reduction of AA, and LTB4 was associated with clinical improvement of psoriasis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

Structural identification of platelet activating factor in psoriatic scale.

Platelet activating factor was isolated from the lesional scale of psoriatic patients using the method described by Bligh and Dyer (8). The extract was subjected to thin layer chromatography, and the region of the plate co-migrating with platelet activating factor removed. A portion of each sample was assayed for aggregating activity using washed guinea-pig platelets and the remainder treated with phospholipase C, derivatised, and subjected to reversed phase high performance liquid chromatography. Fractions were analysed for platelet activating factor using capillary gas chromatography-mass spectrometry. Nanogram quantities of platelet activating factor were recovered from 100 mg scale and both the C16 and C18 alkyl substituents were present in the ratio 3:1, C16:C18.

Animals↗
PubMed1985

Proinflammatory properties of unsaturated fatty acids and their monohydroxy metabolites.

The proinflammatory effects of unsaturated fatty acids and, where appropriate, their monohydroxy derivatives, have been investigated both by application to human skin and with respect to human polymorphonuclear leukocyte (PMN) migration. Of the fatty acids applied to the skin only eicosapentaenoic and arachidonic acids (EPA; AA) produced consistent, measurable erythema. The monohydroxy derivatives of the two fatty acids also caused erythema, the 12-hydroxy isomers being the most potent. Chemokinetic activity towards PMNs was observed in the presence of AA, EPA and alpha-linolenic acid using an agarose microdroplet chemokinesis assay. In contrast to their in vivo properties, the 5-hydroxy isomers of AA and EPA were the most potent, being approximately 10 times more chemokinetically active than the other isomers. Quantification of the hydroxyeicosatetraenoic and hydroxyeicosapentaenoic acids (HETEs; HEPEs) in the lesional skin of psoriatic patients demonstrated that, of the metabolites measured, 12-HETE was present in the greatest amounts. Twenty five times more 12-HETE than 12- or 15-HEPE was detected, these being the most abundant of the HEPEs formed. The monohydroxy derivatives of AA and EPA may contribute to the inflammatory changes observed in psoriasis. The HETEs appear to be of greater importance than the HEPEs in view of the relative amounts present.

Adult↗
PubMed1984

Leukotriene B4-like material in scale of psoriatic skin lesions.

Acidic lipid extracts of scale from the lesions of the skin disease, psoriasis, were purified by straight phase high performance liquid chromatography (h.p.l.c.). Assay of fractions by an agarose microdroplet chemokinesis method showed the presence of biologically active material that coeluted with standard leukotriene B4 (LTB4). LTB4-like chemokinetic activity was also detected in fractions collected on reversed phase h.p.l.c. of psoriatic scale extracts that were initially purified by straight phase h.p.l.c. No LTB4-like activity was detected after similar purification of scale obtained by abrasion of large areas of normal skin. The LTB4-like material found in extracts of psoriatic scale may play a role in the pathogenesis of the neutrophil infiltrate which characterizes psoriasis.

Cell Movement↗
PubMed1982

Leukotriene B4: biological activities and the cytoskeleton.

The aggregation and chemokinesis of either rat or human polymorphonuclear leucocytes (PMNs) induced by leukotriene B4 isomer III (LTB4) are inhibited significantly by colchicine (10(-6) - 10(-3)M) and vinblastine (10(-7) - 10(-4)M). Random migration of the leucocytes is inhibited by colchicine 10(-3)M and vinblastine 10(-4)M. Cytochalasin B (4 X 10(-7) - 4 X 10(-6)M) caused the aggregation of rat PMNs but inhibited their random migration. The aggregation of the PMNs induced by LTB4 was enhanced by cytochalasin B but the chemokinesis was inhibited. It is suggested that both microtubules and microfilaments may be involved in the aggregatory and chemokinetic responses of PMNs to LTB4.

Animals↗
PubMed1981

Aggregation of polymorphonuclear leucocytes (PMNs) by leukotriene B4: effects of cyclooxygenase products and metabolic inhibitors.

Leukotriene B4 isomer III (LTB4) stimulates the aggregation of rat PMNs in vitro. The effects of deoxyglucose, iodoacetate, dinitrophenol, cyclohexamide, colchicine, prostaglandins and thromboxane B2 (TXB2) on aggregation were examined. The results demonstrate that, first, aggregation is an active process, the energy being supplied by glycolysis and not mitochondrial respiration. The response can be elicited in the absence of extracellular glucose. Synthesis of protein does not occur during aggregation. An intact microtubular system is required for the expression of a full aggregation response. Prostaglandins E1, E2, F2 alpha and TXB2, products of the cyclooxygenase pathway of arachidonic acid metabolism, partially inhibit LTB-4 induced aggregation by a mechanism which has not yet been elucidated. The prostaglandins and TXB2 themselves do not promote aggregation.

Alprostadil↗
PubMed1981

Isomers of leukotriene B4 possess different biological potencies.

Rat elicited polymorphonuclear leucocytes (PMNs), when exposed to the ionophore A23187, release three isomers of leukotriene B4. The three isomers have been purified and tested for their ability to induce the chemokinesis of human PMNs in vitro, the aggregation of rat PMNs in vitro and changes in vascular permeability in rabbit skin in vivo in the presence of PGE2. The results demonstrate that all three isomers are biologically active and that the enzymatically produced isomer, in which the conjugated triene contains one cis and two trans double bonds, is more potent than the two diastereoisomers of LTB4 which contain all trans double bonds in the conjugated triene and which are produced by non-enzymatic hydrolysis.

Animals↗
PubMed1981

Leukotriene B4: a mediator of vascular permeability.

1 Intradermal injection of leukotriene B4 (LTB4) or prostaglandin E2 (PGE2), 1 to 100 ng per skin site produced little or no change in plasma exudation in the rabbit, guinea-pig and rat. 2 Intradermal injection of LTB4 or PGE2 together with bradykinin (500 ng) resulted in a significant potentiation of the plasma exudation produced by bradykinin alone in the rabbit and guinea-pig. 4 LTB4 (1 to 10 ng) had no effect on blood flow in the rabbit skin, in contrast to PGE2 which was a potent vasodilator in this species. 5 It is concluded that LTB4 is a mediator of vascular permeability and that this effect can only be observed in the presence of a vasodilator such as PGE2.

Animals↗
PubMed1979

Migration of peritoneal polymorphonuclear leucocytes in the rat.

The migration of PMNs into inflammatory sites in the rat has been studied using elicited peritoneal cells. These cells exhibit normal random migration and phagocytosis in vitro but their chemotactic response towards activated serum is significantly reduced when compared to cells isolated from peripheral blood. When injected intravenously, peritoneal cells not only show a greatly diminished ability to accumulate in inflammatory exudates but also block the migration of peripheral PMNs. Thus while PMNs obtained from the peritoneum may be suitable for some studies, they are not representative of peripheral cells with respect to their ability to accumulate in inflammatory exudates due to implanted inert sponges.

Animals↗
PubMed1978

The effects of D-pencillamine and levamisole on leucocyte chemotaxis in the rat.

The administration of D-penicillamine (25 mg/kg) or levamisole (5 mg/kg) had no effect on leucocyte emigration into the exudates formed in inert sponges implanted in normal rats. 2 In rats, previously sensitized to Bordetella pertussis and implanted with sponges containing pertussis vaccine, an increased leucocyte migration into the exudates occurred; this was significantly enhanced by the administration of the drugs. 3 Neither drug in vitro affected the chemotaxis of rat polymorphonuclear leucocytes although random migration was significantly increased by levamisole (2 microgram to 1 mg/ml). Neither drug affected the chemotaxis of rat mononuclear cells although levamisole (25 microgram/ml) significantly increased that of human monocytes. 4 It is concluded that both drugs produce similar effects in an animal model of delayed hypersensitivity and that their clinical antirheumatic actions may have common elements.

Animals↗