Upregulation of the CD40/CD40 ligand dyad and platelet-monocyte aggregation in cigarette smokers.
BACKGROUND
Smoking is a potent cardiovascular risk factor and is associated with proinflammatory and prothrombotic responses. The CD40/CD40 ligand (CD40L) dyad and platelet-monocyte aggregation mediate a range of proinflammatory and prothrombotic processes thought to be important in atherothrombosis. We investigated whether expression of the CD40/CD40L dyad and platelet-monocyte aggregation are altered in cigarette smokers.


RESULTS
C-reactive protein (CRP), soluble (s) CD40L, and surface expression of CD40L on platelets and T cells and of CD40 on monocytes and platelet-monocyte aggregates were compared in 25 cigarette smokers and 25 age- and gender-matched nonsmokers. Cigarette smokers had increased serum CRP (2.47+/-2.60 versus 0.94+/-0.96 mg/L, P=0.008) and appeared to have elevated plasma sCD40L (0.8+/-1.09 versus 0.37+/-0.21 ng/mL, P=0.07) concentrations. Smokers also had increased surface expression of CD40 on monocytes (45.9+/-7.7% versus 39.9+/-6.5%, P=0.006), of CD40L on platelets (2.9+/-1.0% versus 2.3+/-0.6%, P=0.03), and of platelet-monocyte aggregates (26.6+/-10.9% versus 19.7+/-8.6%, P=0.02). Plasma cotinine concentrations correlated with monocyte CD40 expression, platelet CD40L expression, and platelet-monocyte aggregates.


CONCLUSIONS
Cigarette smokers have upregulation of the CD40/CD40L dyad and platelet-monocyte aggregation that may account for the atherothrombotic consequences of this major cardiovascular risk factor.
Harding
S A
SA
Centre for Cardiovascular Sciences, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
Sarma
J
J
Josephs
D H
DH
Cruden
N L
NL
Din
J N
JN
Twomey
P J
PJ
Fox
K A A
KA
Newby
D E
DE
D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D002097:C-Reactive Protein / Q000032:analysis; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000097:blood / Q000378:metabolism*; D002449:Cell Aggregation; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000502:physiology*; D012907:Smoking / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D015854:Up-Regulation
D019013:CD40 Antigens; D023201:CD40 Ligand; D002097:C-Reactive Protein