Platelet factor 4 in conjunction with IL-4 directs differentiation of human monocytes into specialized antigen-presenting cells

Recent evidence suggests that platelets are not only involved in haemostatic processes but also modulate immune responses. As antigen-presenting cells (APC) are of crucial importance for the regulation of immunity, in this study we wanted to define the role of platelet factor 4 (PF-4) as one of the major platelet-derived chemokines on the transition of monocytes into APCs. Our experiments show that within 3 days PF-4 in conjunction with IL-4 induces a rapid differentiation of monocytes into APC. These PFAPC (PF-4/IL-4 differentiated APC) display unique phenotypical and functional characteristics setting them apart from macrophages and conventional dendritic cells. Functional studies revealed that PFAPC preferentially stimulated proliferation of lymphocytes and lytic NK activity while they induced only moderate cytokine responses. Beyond day 3 of differentiation, PFAPC became less immunostimulatory and maintained their capacity to phagocytose particulate material even after LPS-induced maturation. These experiments uncover a previously unknown role for the platelet-derived CXC-chemokine PF-4 in differentiation of human APC. Our data further support the newly discovered function of platelets in immunomodulation and provide new evidence for a rapid transition of monocytes into APC under the influence of inflammatory stimuli.