Differential influences of gold sodium thiomalate and bucillamine on the generation of CD14+ monocyte-lineage cells from bone marrow of rheumatoid arthritis patients.
An adequate supply of peripheral blood monocytes, granulocytes, and platelets is necessary for an optimal inflammatory process. We have previously demonstrated that the generation of CD14(+) monocyte-lineage cells from the bone marrow is accelerated in patients with rheumatoid arthritis (RA). The current studies examined the influences of gold sodium thiomalate (GST) and bucillamine (BUC), two potent disease-modifying antirheumatic drugs (DMARDs), on the capacity of bone marrow progenitor cells to generate CD14(+) cells in patients with RA, in order to delineate their mechanisms of action. CD14(-) cells purified from bone marrow specimens of 13 patients with active RA who were not taking DMARDs were cultured in the presence or absence of pharmacologically attainable concentrations of GST (25 microM) or intramolecular disulfide form of bucillamine (BUC-ID, 3 microM), a major metabolite of BUC. After incubation for 14 days, the cells were analyzed by flow cytometry for expression of CD14, HLA-DR, and CD54. The generation of CD14(+) cells from RA bone marrow CD14(-) progenitor cells was significantly suppressed by GST, but not by BUC-ID. The expression of HLA-DR on the bone marrow-derived CD14(+) cells was also significantly inhibited by GST, but not by BUC-ID. Of note, neither GST nor BUC-ID influenced the expression of CD54 on the bone marrow-derived CD14(+) cells, indicating that the expression of HLA-DR and CD54 on the bone marrow-derived CD14(+) cells is regulated by different mechanisms. The results are consistent with the hypothesis that one of the effects of DMARDs may involve the interference with monocyte differentiation in the bone marrow. Moreover, the data emphasize that in contrast with BUC, GST is a potent inhibitor of monopoiesis in RA patients.
Hirohata
S
S
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, 173, Japan.
Yanagida
T
T
Hashimoto
H
H
Tomita
T
T
Ochi
T
T
Nakamura
H
H
Yoshino
S
S
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D019070:Cell Lineage / Q000276:immunology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D006052:Gold Sodium Thiomalate; D003545:Cysteine; C026535:bucillamine