CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation.

Abstract:

:CD40 is a 48-kDa phosphorylated transmembrane glycoprotein belonging to the TNF receptor superfamily. CD40 has been demonstrated on a range of cell types, and it has an important role in adaptive immunity and inflammation. CD40 has recently been described on platelets but platelet activation by CD40 has not been described. In the present study, we use flow cytometry and immunoblotting to confirm that platelets constitutively express surface CD40. CD40 mRNA was undetectable, suggesting that the protein is synthesized early in platelet differentiation by megakaryocytes. Ligation of platelet CD40 with recombinant soluble CD40L trimer (sCD40LT) caused increased platelet CD62P expression, alpha-granule and dense granule release, and the classical morphological changes associated with platelet activation. CD40 ligation also caused beta3 integrin activation, although this was not accompanied by platelet aggregation. These actions were abrogated by the CD40L blocking antibody TRAP-1 and the CD40 blocking antibodies M2 and M3, showing that activation was mediated by CD40L binding to platelet CD40. beta3 integrin blockade with eptifibatide had no effect, indicating that outside-in signaling via alphaIIbbeta3 was not contributing to these CD40-mediated effects. CD40 ligation led to enhanced platelet-leukocyte adhesion, which is important in the recruitment of leukocytes to sites of thrombosis or inflammation. Our results support a role for CD40-mediated platelet activation in thrombosis, inflammation, and atherosclerosis.

journal_name

Circ Res

journal_title

Circulation research

authors

Inwald DP,McDowall A,Peters MJ,Callard RE,Klein NJ

doi

10.1161/01.RES.0000070111.98158.6C

subject

Has Abstract

pub_date

2003-05-16 00:00:00

pages

1041-8

issue

9

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000070111.98158.6C

journal_volume

92

pub_type

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