Inhibition of Neutrophil Functions by Platelets and Platelet-Derived Products: Description of Multiple Inhibitory Properties

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Abstract
The effect of platelets and their products on in vitro responses of human neutrophils to f-met-leu-phe (fMLP) and phorbol myristate acetate (PMA) was studied. Platelets produced a concentration-dependent inhibition of neutrophil superoxide anion (O2 -) generation with maximum inhibition of the response to fMLP approaching 42.2 ± 5.4% and that to PMA approaching 85.9 ± 3.4%. Supernates of thrombin-activated platelets produced maximal inhibition of neutrophil O2 - generation in response to fMLP (66.3 ± 4.2%) at a ratio of 10 platelet equivalents (PEQ) to 1 neutrophil but failed to affect the cells' response to PMA. In contrast, lysate of sonicated platelets Inhibited neutrophil O2 - generation in response to both fMLP (59.6 ± 2.0%) and PMA (90.1 ± 1.3 %). Biochemical characterization of platelet lysate identified at least two stimulus-specific inhibitory activities which differ in size, thermal stability and enzyme sensitivity. Platelet lysate also maximally inhibited neutrophil degranulation and chemotaxis at a ratio of 20 PEQ to 1 neutrophil. Our findings indicate that physiologically achievable levels of platelets or their products modulate the response of neutrophils in a stimulus-specific manner and are thereby capable of potentially limiting tissue damage which accompanies neutrophil activation during inflammation.