Conjugation of methotrexate to immunoglobulins kills macrophages by Fc receptor mediated uptake?
The aim of this study was to conjugate methotrexate (MTX) with intravenous immunoglobulin (IVIG) and investigate whether the conjugate produce selective cytotoxicity on macrophages to provide a new strategy for the management of idiopathic thrombocytopenic purpura. MTX was bound to IVIG via human serum albumin as an intermediary. The binding activity of the Fc fragment of the conjugate was assayed by flow cytometry. The selective cytotoxicity of the conjugate was determined by trypan blue exclusion. After conjugating, the binding activity of the conjugate to Fc receptors did not diminish when compared with IVIG. In vitro, the conjugate showed significantly higher cytotoxicity to macrophages than Hela cells. The conjugate of IVIG and MTX showed potent and selective cytotoxicity to macrophages in vitro.
Wang
X
X
Department of Hematology, Cancer Hospital of Tianjin, Tianjin Medical University, Tianjin, China.
Yao
C
C
Jiang
Z
Z
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D006367:HeLa Cells; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D000922:Immunotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy; D011961:Receptors, Fc / Q000276:immunology
D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D011961:Receptors, Fc; D008727:Methotrexate