Macromolecular Activators of Phagocytosis from Platelets ( MAPPs ) and Their Activator Peptide , HATKTAK

Small and large macromolecular activators of phagocytosis from platelets (S-MAPP and L-MAPP, respectively) are released from activated platelets and enhance Fcγ receptor-mediated phagocytosis by neutrophils. Platelets stored in the form of platelet concentrates lose their MAPPproducing activity within 48 h, but recover it when incubated in dialyzed plasma against PBS and supplemented with Ca++. Experiments using expired platelet concentrates revealed that dimer and tetramer holo-transferrin (TF2 and TF4, respectively) function as precursors of MAPPs, while those using platelet lysates showed that MAPPs are activated by the peptide, HATKTAK, which is cleaved from apolipoprotein CIII on high-density lipoproteins (HDL). Experiments on the production of artificial MAPPs by incubating TF2 and TF4 rich solutions with HATKTAK suggested that the binding of HATKTAK and transferrin occurs between the C-terminal K of HATKTAK and sialic acid at the end of the sugar residue of transferrin. Native MAPPs function in the presence of plasma, whereas artificial MAPPs do not. Differences between native and artificial MAPPs may result in artificial MAPPs being more vulnerable to damage by plasma. An immunohistochemical study using an antibody against HATKTAK revealed the wide spread distribution of positive reactions in the human body; therefore, HATKTAK appears to play some roles in biological reactions other than lipid metabolism. Since the amino acid sequence HATKTAK has only been found in primates, the reaction of HATKTAK may be specific to these animals.