Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes.
BACKGROUND
Activated platelets exert a pro-inflammatory action that can be largely ascribed to their ability to interact with leukocytes and modulate their activity. We hypothesized that platelet activation and consequent formation of monocyte-platelet aggregates (MPA) induces a pro-inflammatory phenotype in circulating monocytes.


RESULTS
CD62P(+) platelets and MPA were measured, and monocytes characterized, by whole blood flow cytometry in healthy subjects, before and two days after receiving influenza immunization. Three monocytic subsets were identified: CD14(+)CD16(-), CD14(high)CD16(+)and CD14(low)CD16(+). The increase in high sensitivity C-reactive protein post-immunization was accompanied by increased platelet activation and MPA formation (25.02±12.57 vs 41.48±16.81; p = 0.01), along with enhancement of circulating CD14(high)CD16(+) cells (4.7±3.6 vs 10.4±4.8; p = 0.003), their percentage being linearly related to levels of CD62P(+)-platelets (r(2) = 0.4347; p = 0.0008). In separate in vitro experiments, co-incubation of CD14(+)CD16(-) cells, isolated from healthy donor subjects, with autologous platelets gave rise to up-regulation of CD16 on monocytes as compared with those maintained in medium alone (% change in CD14(+)CD16(+) cells following 48 h co-incubation of monocytes with platelets was +106±51% vs monocytes in medium alone; p<0.001). This effect correlated directly with degree of MPA formation (r(2) = 0.7731; p<0.0001) and was associated with increased monocyte adhesion to endothelial cells. P-selectin glycoprotein ligand-1 (PSGL-1) blocking antibody, which abrogates MPA formation, abolished these effects, as did the cyclooxygenase (COX)-2 selective inhibitor NS-398, aspirin and the EP1/EP2-selective antagonist AH6809.


CONCLUSIONS
These data suggest that MPA formation, as occurs in the blood under pro-inflammatory conditions, expands the pool of circulating CD14(high)CD16(+) monocytes in a COX-2 dependent manner, and these monocytes exhibit increased adhesion to endothelium. Our findings delineate a novel mechanism underlying the pro-inflammatory effect of platelet activation.
Cardiovascular Division, Department of Clinical Pharmacology, King's College London, London, United Kingdom.
Gabriella
G
Passacquale
Padman
P
Vamadevan
Luis
L
Pereira
Colleen
C
Hamid
Valerie
V
Corrigall
Albert
A
Ferro
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002449:Cell Aggregation / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007114:Immunization; D007249:Inflammation / Q000473:pathology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects; D017452:Receptors, IgG / Q000378:metabolism
D017077:Culture Media, Conditioned; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone