Platelet-mediated Leukocyte Activation In Acute Coronary Syndromes

Objective:Platelet-leukocyte interaction and inflammation play important roles in the pathogenesis of acute coronary syndromes. This study was designed to quantify the upregulation of MAC-1 (CD11b/CD 18) and the shedding of L-selectin on neutrophils in response to activatated platelets, and further to explore activated platelet-mediated leukocyte activation in an acute coronary syndrome.Method:Flowcytometry analyses were performed in whole blood to detect the expression of MAC-1 and L-selectin on neutrophils and the activation of T-lymphocytes.Results:With platelets, thrombin receptor agonist peptide (TRAP) induced upregulation of MAC-1 and shedding of L-selectin in a concentration related manner. TRAP effects reached a plateau at a concentration of 5μM, and MAC-1 upregulation approached the upregulation induced with fMLP (100 nM), a leukocyte agonist. However, depletion of platelets from blood prevented all TRAP effects of inducing MAC-1 upregulation and L-selectin shedding. On the other hand, the platelet release products could induce the upregulation of MAC-1 and the shedding of L-selectin as well, while incubation of washed activated platelets with neutrophils did not modify MAC-1 and L-selectin expression in spite of leading to the formation of platelet-neutrophil co-aggregates. In addition, upregulation of MAC-1 and shedding of L-selectin in response to TRAP stimulation were directly corelated with platelet counts, and the effects approached to the maximal at physiological counts of platelets.Compared to patients with stable angina or healthy volunteers, the MAC-1 expession on PMN in STEMI (ST-elevation mycardial infarction) patients exist a tendency of rise. TRAP(10μM)-induced upregulation of MAC-1 on nutrphils in patients with STEMI was much greater than those in patients with stable angina or normal volunteers (all P<0.01). More over, the expression of HLA-DR on T-lymphocytes as well as leukocyte counts in STIME patients were much higher than those in patients with stable angina and healthy volunteers (all P<0.01).Conclusion:①Activated platelets induced MAC-1 upregulation and L-selectin shedding on nutrophils by platelet release products.②Nutrophils in STEMI were hyper-responsive to platelet agonist, while expression of HLA-DR on T-cells in ACS enhanced, in line with increased number of white cell counts.