Platelet aggregation is inhibited by a nitric oxide-like factor released from human neutrophils in vitro.
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 monophosphate (cyclic GMP) phosphodiesterase inhibitor. Haemoglobin lessened this inhibitory action of neutrophils. L-Arginine, the substrate for nitric oxide formation, enhanced inhibition, whereas, L-canavanine, a structural analogue of L-arginine, prevented it. Nitric oxide release by neutrophils antagonized platelet ATP secretion and thromboxane B2 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-leu-phe, there was a further increase in platelet cyclic GMP. This was enhanced by superoxide dismutase, but lessened by haemoglobin. Leukotriene B4 stimulation of neutrophils promoted inhibition of platelet aggregation. Leukotriene B4 alone had no direct effect on thrombin-induced aggregation of platelets. Platelets, when incubated with neutrophils and stimulated with calcium ionophore A23187, increased leukotriene B4 production by neutrophils in a platelet concentration dependent manner. Platelets alone were unable to release leukotriene B4. The action of platelets in haemostasis is modified as they come into contact with neutrophils. This may be an important physiological mechanism.
Faint
R W
RW
Department of Haematology, Middlesex Hospital, London.
Mackie
I J
IJ
Machin
S J
SJ
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000255:Adenosine Triphosphate / Q000097:blood; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000097:blood; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D009569:Nitric Oxide / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood
D010975:Platelet Aggregation Inhibitors; D007975:Leukotriene B4; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000255:Adenosine Triphosphate; D006152:Cyclic GMP