A MONOCYTE CHEMOTACTIC FACTOR, S19 RIBOSOMAL-PROTEIN DIMER, IN PHAGOCYTIC CLEARANCE OF APOPTOTIC CELLS

HL-60 cells derived from a human promyelocytic leukemia underwent apop tosis by heat treatment. When the heat-treated HL-60 cells were inject ed into guinea pig skin, monocyte/macrophage infiltration was observed 24 or 36 hours later, and the apoptotic cells were phagocytically cle ared by 48 hours after their injection. The infiltration and clearance patterns were quite different from those observed in injection of nec rotic or boil-fixed HL-60 cells. The apoptotic cells released a monocy te chemotactic factor in vitro 24 hours after the heat treatment. The chemotactic factor generated was identified as the cross-linked homodi mer of S19 ribosomal protein by its immunologic and physicochemical pr operties. A serine protease that inactivates the monocyte chemotactic factor was also released from the apoptotic cells 30 hours after the h eat treatment. A Super infusion of this protease into the skin where t he apoptotic cells had been injected diminished the number of infiltra ted monocytes. The present results indicate an important role of the S 19 ribosomal protein dimer in the phagocytic clearance of apoptotic ce lls.