Degradation of platelet glycoprotein Ib by elastase released from primed neutrophils.
Mutual interactions between neutrophils (PMN) and platelets are recognized to be important in modulating the respective functions of these two cell types. Here we show that primary granule secretion from appropriately-stimulated PMN can lead to complete proteolytic removal of GPIb from the platelet surface. Thus, when the PMN in PMN/platelet mixtures were stimulated by FMLP, platelets lost GPIb as measured by ristocetin-induced aggregation, flow cytometry and SDS-PAGE analysis. This loss was most marked when PMN were primed by GM-CSF, and could be inhibited by a specific elastase inhibitor. As expected, the alpha 1-antiproteinase in plasma inhibited GPIb loss, but when PMN were strongly stimulated by FMLP and GM-CSF in the presence of platelets this inhibition was incomplete or absent. It is concluded that joint priming of PMN with GM-CSF and platelets can cause a previously unrecognized degree of primary granule secretion which, via elastase, leads to platelet GPIb loss. We suggest that this loss is likely to be of physiological and pathophysiological importance.
Aziz
K A
KA
Department of Haematology, University of Liverpool.
Cawley
J C
JC
Kamiguti
A S
AS
Zuzel
M
M
D001792:Blood Platelets / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012310:Ristocetin / Q000494:pharmacology
D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C028254:von Willebrand factor receptor; D012310:Ristocetin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase