Faint, Richard William; (1992) Platelet-neutrophil interaction: neutrophils modulate platelet function. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Platelets are vital for the arrest of bleeding following tissue injury. Neutrophils play an important role in host defence against bacterial infection. In the milieu of the acute inflammatory response both cellular and non-cellular elements may interact to modify behaviour. Evidence suggests that leukocytes may play an active role in the modulation of platelet function. This interaction may be abnormal in certain pathological states. This study examined the effect of purified neutrophils upon both washed platelets and platelet-rich plasma, as well as in whole blood in vitro. Neutrophils were found to alter platelet behaviour by several mechanisms. These included transcellular metabolism of eicosanoids. Neutrophils utilized platelet-derived arachidonate to release increased amounts of leukotrienes. Other arachidonate metabolites resulted from platelet-neutrophil interaction and these differed quantitatively and qualitatively from those arising from either cell-type alone. Another mechanism was the release of a nitric oxide-like factor by neutrophils. Nitric oxide inhibits platelet adhesion and aggregation via guanylate cyclase stimulation. Platelet ATP secretion and TXBj release were also impaired. The effect of authentic nitric oxide in whole blood was investigated. Platelet aggregation in whole blood, in the presence of L-arginine (the substrate for nitric oxide synthesis), was found to be inhibited by a nitric oxide-like factor. Neutrophils, under different conditions, were potent inducers of platelet calcium flux, aggregation and secretion. This activity was mediated by a neutrophil-derived protease, most likely to be cathepsin G. These different mechanisms of platelet-neutrophil interaction were investigated in patients with Multiple System Organ Failure Syndrome, where clinical observations have implicated both platelet and neutrophil involvement. Some patients exhibited platelet-neutrophil interaction abnormalities. The interaction of platelets with neutrophils may help to explain some of the pathophysiological events associated with different clinical states.

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