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Platelet aggregation is inhibited by a nitric oxide‐like factor released from human neutrophils in vitro
Author(s) -
Faint R. W.,
Mackie I. J.,
Machin S. J.
Publication year - 1991
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1991.tb08623.x
Subject(s) - nitric oxide , chemistry , leukotriene b4 , platelet , superoxide , thrombin , biochemistry , cyclic guanosine monophosphate , pharmacology , medicine , enzyme , biology , inflammation , organic chemistry
S ummary . Thrombin‐induced platelet aggregation was inhibited in vitro by washed human neutrophils. Aggregation was inhibited in a neutrophil concentration dependent manner but glutaraldehyde fixed neutrophils had no significant effect on platelet aggregation. The neutrophil‐derived inhibitory factor had the pharmacological profile of nitric oxide. Its action was potentiated by both superoxide dismutase and M&B22, 948, a selective cyclic guanosine mono‐phosphate (cyclic GMP) phosphodiesterase inhibitor. Haemoglobin lessened this inhibitory action of neutrophils. L‐Arginine, the substrate for nitric oxide formation, enhanced inhibition, whereas, manavanine, a structural analogue of L‐arginine, prevented it. Nitric oxide release by neutrophils antagonized platelet ATP secretion and thromboxane B 2 release. Inhibition was mediated by nitric oxide activation of guanylate cyclase with a subsequent rise in cyclic GMP. When neutrophils were stimulated with formyl‐met‐leuphe, there was a further increase in platelet cyclic GMP. This was enhanced by superoxide dismutase, but lessened by haemoglobin. Leukotriene B 4 stimulation of neutrophils promoted inhibition of platelet aggregation. Leukotriene B 4 alone had no direct effect on thrombin‐induced aggregation of platelets. Platelets, when incubated with neutrophils and stimulated with calcium ionophore A23187, increased leukotriene B 4 production by neutrophils in a platelet concentration dependent manner. Platelets alone were unable to release leukotriene B 4 . The action of platelets in haemostasis is modified as they come into contact with neutrophils. This may be an important physiological mechanism.