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Interaction of human platelets and leukocytes in modulation of vascular tone
S Kaul1, B J Waack, R C Padgett
1Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Abstract:
We tested the hypothesis that the vasodilator response to human platelets is modulated by polymorphonuclear leukocytes (PMNs). Responses to platelets activated with thrombin, as well as PMNs activated with N-formylmethionyl-leucyl-phenylalanine (FMLP), were examined in perfused rabbit carotid arteries in vitro. Activation of platelets produced marked dilatation, and activation of PMNs produced modest constriction in arteries preconstricted with phenylephrine. Vasodilator responses to platelets were greatly impaired during infusion of activated PMNs. Pretreatment of PMNs with superoxide dismutase (SOD) partially restored dilator responses to platelets. Because SOD only partially restored vasodilator responses to platelets, we tested the possibility that adenosine-diphosphatase (ADPase) activity of PMNs may degrade ADP released by platelets and thus reduce vasodilator responses. After incubation with PMNs, dilator responses to ADP, but not acetylcholine, were significantly impaired. These findings indicate that vasodilatation produced by activated human platelets is profoundly impaired by activated leukocytes. We conclude that two mechanisms may account for this effect: 1) endothelium-derived relaxing factor, released in response to platelet-derived ADP, is inactivated by superoxide anion generated by activated PMNs and 2) ADP is degraded by ADPase activity of PMNs. We speculate that platelet-leukocyte interaction may have important effects on vasomotor tone.
Insights
Activated leukocytes impair platelet-induced vasodilation. This occurs because superoxide anions from leukocytes inactivate endothelium-derived relaxing factor and leukocyte enzymes degrade platelet-released ADP, impacting blood vessel tone.
Area of Science:
- Cardiovascular Physiology
- Hematology
- Immunology
Background:
- Platelets are known to induce vasodilation.
- Leukocytes, particularly polymorphonuclear leukocytes (PMNs), can influence vascular tone.
- The interaction between platelets and leukocytes in modulating vascular responses is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that polymorphonuclear leukocytes (PMNs) modulate the vasodilator response to human platelets.
- To elucidate the mechanisms by which activated PMNs affect platelet-mediated vasodilation.
Main Methods:
- Utilized an in vitro perfused rabbit carotid artery model.
- Examined responses to thrombin-activated platelets and N-formylmethionyl-leucyl-phenylalanine (FMLP)-activated PMNs.
- Assessed the impact of PMN infusion on platelet-induced vasodilation and the effects of superoxide dismutase (SOD) and adenosine-diphosphatase (ADPase) inhibition.
Main Results:
- Activated platelets induced significant vasodilation, while activated PMNs caused modest constriction.
- Platelet-induced vasodilator responses were markedly impaired in the presence of activated PMNs.
- Superoxide dismutase (SOD) partially restored platelet-mediated vasodilation.
- PMN incubation impaired vasodilator responses to adenosine diphosphate (ADP) but not acetylcholine, suggesting ADP degradation by PMNs.
Conclusions:
- Activated leukocytes profoundly impair vasodilatation mediated by activated human platelets.
- Two primary mechanisms contribute to this impairment: inactivation of endothelium-derived relaxing factor by PMN-generated superoxide anions and degradation of platelet-derived ADP by PMN ADPase activity.
- Platelet-leukocyte interactions may significantly influence vasomotor tone.