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M Chignard

Publications and source records attributed to M Chignard.

98 records · Page 6Linked to original sources
PubMed1975

Substances that increase the cyclic AMP content prevent platelet aggregation and the concurrent release of pharmacologically active substances evoked by arachidonic acid.

Arachidonic acid-induced platelet aggregation was inhibited by prostaglandins E1 and F2alpha(PGE1 and PGF2alpha), papaverine and dibutyryl cycle AMP. Prostaglandin E2 displayed a biphasic effect, as concentrations below 2 muM potentiated aggregation, whereas concentrations above it were inhibitory. Isoproterenol (up to 10 mM) failed to block aggregation but inhibition was uncovered in presence of adrenergic alpha-blocking agents. Isoproterenol potentiated aggregation due to sub-threshold amounts of arachidonic acid, and this effect, but not that due to PGE2, was suppressed by the alpha-blocking agents. Isoproterenol and PGE2 appear thus to enhance arachidonic acid-induced platelet aggregation after interacting with different receptor sites. The yield of rabbit aorta contracting activity formed during AA-induced aggregation was markedly reduced by PGE1, dibutyryl cyclic AMP and high concentrations of PGE2, and was increased by low concentrations of the latter. PG-like activity was not significantly reduced when aggregation and generation of rabbit aorta contracting activity were inhibited by bibutyryl cyclic AMP. It is hypothesized that interaction of human platelets and arachidonic acid results in formation of different pharmacologically active materials, possibley bearing similar lipoperoxide structures. Generation of one portion of these materials is controlled by the adenyl cyclase-cyclic AMP system, whereas another portion, that comprises the natural PG, is cyclic AMP-independent. Prostaglandins formed during platelet aggregation have a regulatory role and modulate the platelet response, rather than constitute a trigger stimulus for aggregation.

Animals↗
PubMed1975

Blockade by metal complexing agents and by catalase of the effects of arachidonic acid on platelets: relevance to the study of anti-inflammatory mechanisms.

Metal-chelating agents inhibited platelet aggregation and the accompanying generation of rabbit aorta contracting and PG-like activities, when platelets were challenged with arachidonic acid. Inhibition required the presence of the chelating agents in the medium, and was insured by reagents avid for free or protein-bound copper. Catalase also prevented aggregation and generation of pharmacologically active substances; its activity was reversed by aminothiol agents and by Cu2+ and Zn2+, shown previously to potentiate the platelet effects of arachidonic acid. Inhibition by indomethacin was not prevented by amino-thiol drugs nor by Cu2+ or Zn2+. The catalase-induced inhibition was not affected by scavenging of thiol groups; this rules out, as a mechanism of action of catalase, the increased destruction of popoperoxides by glutathione peroxidase, which requires reduced glutathione as hydrogen donor. The results are compatible with the hypothesis that the agent that mediates platelet aggregation by arachidonic acid is a popoperoxide, requiring the presence either of H2O2 or of a similarly catalase-sensitive substance to be generated.

Adenosine Diphosphate↗
PubMedDate not supplied

Exercise- and allergen-induced asthma do not change the production of Paf-acether by neutrophils and platelets.

Paf-acether, whose role has been suggested in asthma, is a mediator released by stimulated neutrophils, platelets and other cells. Neutrophils and platelets are activated in vivo during exercise or allergen-induced asthma. Upon in vitro stimulation, macrophages from mice treated with an inflammatory stimulus, such as thioglycoccollate, release less paf-acether than macrophages from non-treated mice. We hypothesized that upon in vitro activation platelets and neutrophils should produce less paf-acether after exercise- or allergen-induced asthma. To test this hypothesis, we measured the production of paf-acether by neutrophils and platelets obtained before, 15 and 75 min after exercise in seven normal subjects and five asthmatic subjects with exercise-induced asthma, and in five other asthmatic subjects after specific challenge with Dermatophagoides Pteronyssinus. Purified neutrophils and washed platelets were incubated independently for 10 min at 37 degrees C with no specific activator, with a platelet activator (thrombin, 1 IU.ml-1), a neutrophil activator (opsonized zymosan, 1 mg.ml-1), and both together. We found no significant difference between asthmatic and normal subjects in the amount of paf-acether synthesized by platelets or neutrophils and no fall in the production of paf-acether after exercise- or allergen-induced asthma. However, our method may lack sensitivity in detecting partial activation of these cells and is based on the assumption that changes in peripheral blood cells are representative of changes of these cells in lungs.

Adult↗
PubMedDate not supplied

[Platelet aggregation and platelet activating factor (author's transl)].

Platelet aggregation is triggered by at least three distinct pathways. The first one is mediated by adenosine diphosphate, the second one by arachidonic acid metabolites and the third is defined somehow by exclusion of the first two. In fact rabbit platelets synthesize, during their activation, another substance with potent aggregating activity, namely platelet-activating factor or PAF-acether. Indirect pieces of evidence are presented, which suggest that PAF-acether is the mediator of the third pathway of platelet aggregation.

Animals↗
PubMedDate not supplied

Synergism between interleukin-8 and tumor necrosis factor-alpha for neutrophil-mediated platelet activation.

We previously showed that two polymorphonuclear neutrophil (PMN)-derived proteinases, namely cathepsin G (Cat. G) and elastase (HLE), acting in synergy activated nearby platelets in vitro. This cellular interaction could result in a pathology such as the adult respiratory distress syndrome (ARDS). Since elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were detected in these patients and therefore could be involved in this disease, we looked for their effects in the PMN-platelet cooperation system. Addition of IL-8 to mixed suspensions of PMN and platelets induced weak but significant platelet aggregations. Upon preincubation with TNF-alpha, aggregations triggered by IL-8 were significantly increased. The targets of these cytokines were not the platelets but the PMNs. This was shown by following beta-glucuronidase release and more interestingly by measuring the enzymatic activities of Cat. G and HLE in the supernatant. Inhibition of the platelet response upon addition of a serine proteinase inhibitor, eglin C, clearly demonstrated the involvement of these two enzymes. Taken together, these results constitute an additional argument for the role of the PMN-platelet interaction in ARDS.

Adult↗