Shahbazi, Touran; (1997) Engagement of platelet integrins "β3" and "β1". triggers two distincts signal pathways with different susceptibilities to nitric oxide. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The areas of human washed platelets, visualised by interference reflection microscopy, attaching and spreading on glass coated with either fibrinogen, fibronectin or collagen were measured by digital video image processing techniques. Platelet attachment and spreading on fibrinogen was strongly inhibited by the nitric oxide (NO) donors at all concentrations used. These NO donors inhibited cell attachment and spreading on collagen at the highest concentration tested (100μM) and on fibronectin, virtually no inhibitory effect was observed. The anti-attachment/spreading effect of all NO donors was prevented by oxy-haemoglobin, confirming that NO release was the cause of inhibition. Exposure of already attached platelets to NO donors caused platelets to lose their dark close contacts with the surface suggesting that they were lifting off the substrate. This phenomenon was only observed on fibrinogen. Pre-treatment of platelets with anti-glycoprotein Ilb/IIIa antibody prevented attachment and spreading on fibrinogen. On fibronectin, exposure of antibody treated platelets to NO donors had no effect and did not cause any loss of close contact. Studies using NO donors, a range of protein kinase and phospholipase inhibitors and activators and acetyl salicylic acid showed that distinct signal pathways were involved in attachment and spreading on fibrinogen and fibronectin. Both pathways converged at the activation of protein kinase C. Sodium nitroprusside inhibited only the pathway activated by fibrinogen binding and had no effect on fibronectin. Acetylsalicylic acid and 4-bromophenacyl bromide inhibited attachment and spreading on fibrinogen but had no effect on fibronectin. In common with cell attachment on fibrinogen, phorbol ester potentiated attachment on fibronectin as on fibrinogen. The results showed that the signal pathway leading from integrin engagement of fibronectin was different to that of fibrinogen possibly due to clustering of a different set of receptors.

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