Immature myeloid dendritic cells capture and remove activated platelets from preformed aggregates

Background: Immature dendritic cells (DCs) patrol the circulation, where they can uptake antigens. It has been reported that mature monocyte-derived DCs have the ability to interact with an activated platelet monolayer under high shear conditions (1500 s-1). Objectives: In this study, we investigated whether platelets can recruit immature myeloid DCs (CD1c+) directly isolated from blood (BDCs) and if so, which receptors are involved. Results: Using flow cytometry and electron microscopy, we showed that BDCs interact with activated but not resting platelets in suspension. Interaction was also observed after perfusing BDCs under low flow conditions (150 s-1) through collagen-coated microcapillaries in which platelets had adhered and formed aggregates. No such interaction could be detected at higher shear rates. Whereas initial transient attachment required the exposure of P-selectin on activated platelets and PSGL-1 on BDCs, subsequent stationary adhesion was dependent on alpha(IIb)beta(3) and alpha(M)beta(2) integrins on platelets and BDCs, respectively. Moreover, during their transient interaction, BDCs preferentially removed platelets located at the outer margin of the thrombus in a P-selectin- and integrin-dependent manner. Conclusion: This study provides evidence for an interaction between activated platelets and immature myeloid DCs only under low shear conditions. This could be of importance for BDC maturation and antigen uptake during normal hemostasis or in the context of atherothrombosis at sites of reduced blood flow.