Platelet senescence and death.
The factors controlling the lifespan of platelets both in vivo and in vitro are poorly understood. What is known is that platelet aging in vivo leads to a reduction in the platelets' responsiveness to physiological agonists and that younger platelets are more haemostatically active than older ones. Under in vitro and ex vivo conditions platelets also lose function and ultimately die for reasons that are unclear, by mechanisms that share some similarity with those used by nucleated cells for programmed cell death. The consequences of platelet death in vitro include the formation of a novel platelet-platelet interaction that occurs between dead but not viable platelets and the shedding of the collagen receptor, GPVI and CD42b, a component of the von Willebrand receptor complex. Both of these phenomena appear to be regulated by metalloproteinase activity. In addition to these observations it is becoming increasingly clear that platelets execute a novel form of programmed cell death in response to agonists such as collagen and thrombin suggesting that their death is intimately associated with effective haemostasis. Finally, platelets must be removed from circulation. It is unclear how senescent platelets are removed, but monocyte-macrophages are an important determinant of thrombus resolution possibly due to the phagocytosis of effete, activated platelets.
Hartley
Paul S
PS
Circadian Physiology Group, Centre For Cardiovascular Science, University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK. Phartle1@staffmail.ed.ac.uk
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D016923:Cell Death; D016922:Cellular Senescence; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D003094:Collagen; D045726:Metalloproteases; D013917:Thrombin