Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia

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Abstract
The phagocytosis of pathogens is a critical event in host defense, not only for clearance of the invading microorganism, but also for the subsequent immune response. We have examined Dectin-1, a proinflammatory nonopsonic receptor for β-glucans, and show that it mediates the internalization of β-glucan-bearing ligands, including yeast particles. Although requiring tyrosine phosphorylation and the cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM)-like motif, uptake mediated by Dectin-1 was different from any previously reported phagocytic receptor and was not dependent on Syk-kinase in macrophages. Furthermore, intracellular trafficking of this receptor was influenced by the nature of the β-glucan ligand, which has significance for the biologic activity of these immunomodulatory carbohydrates. (Blood. 2004;104:4038-4045)