A monocyte specific chemotactic factor, S19 ribosomal protein homodimer, was originally isolated from rheumatoid arthritis-synovial tissue. The homodimer but not the monomer shared an immunologic epitope with the complement-derived leukocyte chemotactic factor, C5a. The monocyte chemotactic effect of the S19 protein homodimer was inhibited by an anti-C5a receptor monoclonal antibody or by a synthetic C5a receptor antagonist. The S19 protein homodimer competitively inhibited the binding of radiolabeled C5a to polymorphonuclear leukocytes. Furthermore, the S19 protein homodimer inhibited the chemotactic response of polymorphonuclear leukocytes to C5a in vitro and in vivo. These data indicate that the S19 protein homodimer possess a three-dimensional structure similar to C5a in terms of the receptor ligand, although homology between their primary structures is only 4%. The S19 protein homodimer with these opposite effects in the leukocyte chemotaxis, agonistic to monocytes and antagonistic to polymorphonuclear leukocytes, seems to be a factor to induce the monocyte/macrophage predominant infiltration in chronic inflammation.
Kupffer cells were selectively eliminated in the macrophage colony stimulating factor (M-CSF)-deficient osteopetrotic (op/op) mice by intravenous administration of liposome-entrapped dichloromethylene diphosphonate. Repopulation of Kupffer cells was observed in the Kupffer cell-depleted littermate mouse (op/+) liver by 14 days after treatment. In contrast, repopulation of Kupffer cells was not observed in the Kupffer cell-depleted op/op mice through the observation period of 56 days. Daily administration of M-CSF induced remarkable repopulation of Kupffer cells and proliferation of macrophage precursor cells, whereas GM-CSF and IL-3 were less effective. These findings indicated that M-CSF plays a major role in Kupffer cell development.
A 68-year-old female was hospitalized because of general fatigue and edema. Physical examination revealed anemia and splenomegaly, and laboratory tests showed severe hypoproteinemia and pancytopenia. She was splenectomized and diagnosed as histiocytic sarcoma showing diffuse infiltration of large histiocytic cells (LCA-, CD45RO-, CD20-, CD15-, CD30-, CD35-, CD68+ FDC+, fascin+). While any test including gastrointestinal endoscopy and bone marrow cytology did not detect infiltration of the sarcoma cells, hypoproteinemia and pancytopenia continued after splenectomy. An alpha anti-trypsin test revealed protein-losing gastroenteropathy. Despite of CHOP therapy-resistance, treatment with etoposide and prednisolone improved hypoproteinemia and pancytopenia.