Small-size platelet microparticles trigger platelet and monocyte functionality and modulate thrombogenesis via P-selectin.
This study aimed to examine the mechanisms of cellular activation by small-size platelet microparticles (sPMP) and to present the performance of high-resolution flow cytometry for the analysis of subcellular entities from different origins. Plasma counts of sPMP were analysed in coronary artery disease patients (n = 40) and healthy controls (n = 40). The effect of sPMP and platelet debris (PD) in pathophysiologically relevant doses on platelet and monocyte activation parameters and thrombogenesis was investigated via flow cytometry and thromboelastometry. New generation flow cytometry identifies differences in size, levels and surface molecules of sPMP derived in the absence of stimulus, thrombin activation and platelet disruption. Addition of sPMP resulted in platelet degranulation and P-selectin redistribution to the membrane (P = 0·019) in a dose and time-dependent manner. Blood clotting time decreased after addition of sPMP (P = 0·005), but was not affected by PD. Blocking P-selectin (CD62P) in sPMP markedly reverted the effect on thrombus kinetics (P = 0·035). Exposure to sPMP stimulated monocyte expression of intercellular adhesion molecule-1 (P < 0·03) and decreased monocyte interleukin-6 receptor density (P < 0·01). These results implicate sPMP as a direct source of downstream platelet and monocyte activation. In pathological coronary artery disease conditions, higher levels of sPMP favour a prothrombotic state, partly through P-selectin expression.
University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK; Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain.
Silvia
S
Montoro-García
Eduard
E
Shantsila
Diana
D
Hernández-Romero
Eva
E
Jover
Mariano
M
Valdés
Francisco
F
Marín
Gregory Y H
GY
Lip
D000704:Analysis of Variance; D001777:Blood Coagulation / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism / Q000502:physiology*; D015539:Platelet Activation / Q000502:physiology*; D013916:Thrombelastography; D013917:Thrombin / Q000502:physiology; D013927:Thrombosis / Q000097:blood*
D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D013917:Thrombin
high-resolution flow cytometry; phosphatidylserine and P-selectin exposure; platelet and monocyte activation; small-size microparticles