Summary
Clinical and experimental observations suggest that platelet function deteriorates
quickly with cell age. However, efforts to define agedependent alterations have detected
only modest biochemical changes occurring late in the cell life span. In this report,
we demonstrate two significant alterations of the collagen response occurring during
in vivo aging of canine platelets: a progressive increase in the EC50 for collagen types
I, III and V and the emergence of a population of aged platelets which are refractory
to collagen. Experiments with convulxin, a specific agonist for the collagen receptor
glycoprotein VI (GPVI), also demonstrate an age-dependent decline in activation and
the appearance of a non-reactive, aged population as observed with native collagens.
Our studies indicate that canine platelets have two distinct binding levels for FITC-labeled
convulxin and that the higher binding level disappears upon cell aging. During these
studies one dog (#428) was identified whose platelets not only failed to demonstrate
an age-dependent decrease in convulxin reactivity but also maintained a high convulxinbinding
ability throughout their otherwise normal life span. Transfusion of biotinylated platelets
from control dogs into dog #428 showed that the expected changes in collagen response
and GPVI function did not occur in the transfused platelets. These observations demonstrate
that the canine platelet response towards collagen is strongly dependent upon cell-age
and suggest that this functional decline is at least partly due to an extrinsic-mediated
alteration, possibly proteolytic, of GPVI.
This work was supported in part by grants HL53585 and HL68129 from the National Institutes
of Health (GLD) and the Swiss National Science Foundation (SSMBS grant, LA; grant
31-52396.97, KJC). This work has been presented at the XVIII Congress of the International
Society on Thrombosis and Haemostasis (Paris, 2001).
Keywords
Platelets - collagen - cell-age - P-selectin - flow-cytometry - convulxin - glycoprotein
VI