Thiazolidinediones increase the number of platelets in immune thrombocytopenic purpura mice via inhibition of phagocytic activity of the reticulo-endothelial system.
Thiazolidinediones (TZDs) have broad spectrum of actions, including immunomodulating effects that are dependent or independent of the target nuclear receptor, peroxisome proliferator activated receptor-gamma (PPAR-gamma). In this study, we investigated the effect of TZDs on the platelet numbers in male immune thrombocytopenic purpura (ITP) model mice, (NZW x BXSB)F(1) (W/BF(1)) in vivo, and attempted to clarify the mechanism of action. Seven-day treatment with troglitazone increased platelet counts by 66% compared with those of controls. Within two weeks after the termination of the treatment period, the numbers of platelets were decreased to the level in controls. Pioglitazone showed only weak increasing effect on platelet counts in short-term experiment. However, long-term treatment with the drug resulted in a more pronounced up-regulation of platelets. We next assayed the platelet-associated antibodies (PAA) and the survival rate of antibody-sensitized mouse erythrocytes (Ab-mRBC) in W/BF1 mice. Pioglitazone slightly decreased the production of PAA and significantly elongated the survival period of Ab-mRBC in vivo. These drugs showed dose-dependent inhibitory effects on the cell proliferation and Fcgamma receptor (FcgammaR)-mediated phagocytic activity of macrophage-like cells in vitro. These results suggest that TZDs improve platelet counts in this mouse model mainly by suppressing systemic reticulo-endothelial phagocytic function.
Kasono
Keizo
K
Department of Endocrinology and Metabolism, Jichi Medical School, Omiya Medical Center, 1-847 Amanuma-cho, Saitama 330-8503, Japan.
Nishida
Jyunji
J
Tamemoto
Hiroyuki
H
Fudaka
Kazuko
K
Namai
Kazuyuki
K
Kajio
Hiroshi
H
Masatoshi
Kuroki
K
Kanazawa
Yasunori
Y
Kawakami
Masanobu
M
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D001323:Autoantibodies / Q000032:analysis; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology; D019556:COS Cells; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000276:immunology; D006824:Hybridization, Genetic; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012157:Mononuclear Phagocyte System / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D000077205:Pioglitazone; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
D001323:Autoantibodies; D007004:Hypoglycemic Agents; D011961:Receptors, Fc; D013844:Thiazoles; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione; D000077205:Pioglitazone