Acquired immune response as a consequence of the macrophage-dependent apoptotic cell clearance and role of the monocyte chemotactic S19 ribosomal protein dimer in this connection

A connection between the apoptotic cell clearance system and the acquired i mmune system was studied in vivo. When fluorescence-labeled apoptotic HL-60 cells were inoculated into footpads of guinea pigs and rabbits, monocyte/m acrophage infiltration rapidly occurred and subsequently the apoptotic cell s as well as the macrophages disappeared from the lesion by 48 hours withou t any macroscopical signs of inflammation. Inversely, the fluorescent cell debris, which had been engulfed by the macrophages, appeared and chronologi cally increased in the draining lymphatics and the popliteal lymph nodes by 48 hours. Subsequently, proliferation of T and B lymphocytes in the poplit eal lymph nodes was observed. Secondary inoculation of HL-60 cells in the f lank skin of guinea pigs on day 3 after the initial inoculation induced an acute immunologic dermatitis with erythema, edema, vascular permeability en hancement, and polymorphonuclear leukocyte infiltration. In vitro character izations demonstrated the presence of compliment dependent cytotoxic IgM an tibody against HL-60 cells in their sera. The infiltration of monocytes/mac rophages at the apoptotic cell injection site and the subsequent production of the anti-HL-60 cell IgM antibodies were significantly suppressed by in situ injections of anti-Sig ribosomal protein rabbit antibodies. These resu lts indicated that the serial events with the rapid apoptotic cell clearanc e by macrophages, the macrophage migration to lymph nodes, and the antigen presentation to T lymphocytes by the macrophages acquire immunity against a poptotic cells. It was also indicated that the S19 ribosomal protein dimer was the major chemotactic factor in the initial monocyte/macrophage infiltr ation to apoptotic cells.