Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes.

Area of Science:

• Immunology
• Hematology
• Inflammation Research

Background:

• Activated platelets contribute to inflammation by interacting with leukocytes.
• Platelet activation and monocyte-platelet aggregate (MPA) formation are hypothesized to induce a pro-inflammatory monocyte phenotype.

Purpose of the Study:

• To investigate the role of MPA formation in inducing a pro-inflammatory phenotype in circulating monocytes.
• To explore the mechanisms underlying platelet-induced monocyte activation and their functional consequences.

Main Methods:

• Whole blood flow cytometry was used to measure CD62P(+) platelets and MPA in healthy subjects post-influenza immunization.
• Monocyte subsets (CD14(+)CD16(-), CD14(high)CD16(+), CD14(low)CD16(+)) were characterized.
• In vitro co-incubation of monocytes with platelets was performed, with interventions including P-selectin glycoprotein ligand-1 (PSGL-1) blocking antibody, cyclooxygenase (COX)-2 inhibitor NS-398, aspirin, and EP1/EP2 antagonist AH6809.

Main Results:

• Influenza immunization increased platelet activation, MPA formation, and the proportion of circulating CD14(high)CD16(+) monocytes.
• The percentage of CD14(high)CD16(+) cells correlated with CD62P(+) platelet levels.
• In vitro, platelet co-incubation induced CD16 upregulation on monocytes, increasing their adhesion to endothelial cells, an effect abrogated by PSGL-1 blockade and COX-2 inhibition.

Conclusions:

• MPA formation under pro-inflammatory conditions expands circulating CD14(high)CD16(+) monocytes in a COX-2 dependent manner.
• These monocytes exhibit enhanced adhesion to the endothelium.
• This study delineates a novel mechanism for the pro-inflammatory effects of platelet activation.