Recipient humoral immunity against leukoreduced allogeneic platelets is suppressed by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase
Recipient humoral immunity against leukoreduced allogeneic platelets is suppressed by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase
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DOI：
10.1182/blood.v88.8.2959.bloodjournal8882959
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发表时间：
1996-10-15
期刊：
影响因子：
20.3
通讯作者：
Semple, JW
中科院分区：
文献类型：
--
作者：
Bang, A;Speck, ER;Semple, JW
先前已显示白细胞减少的同种异体血小板输注最初刺激体外细胞毒性，随后诱导免疫球蛋白G（IgG）抗供体同种抗体的形成。为了进一步表征这些反应并确定它们是否相关，受体BALB/c H-2（d）小鼠用氨基胍（AMG）（诱导型一氧化氮合酶（iNOS）的选择性抑制剂）处理，每周输注2 x 10（8）C57 BL/6 H2（B）血小板。在对照组、非AMG处理的小鼠中，输血显著（P <0.01）增加了输血后第1天（PT）的干扰素-γ（IFN-γ）血清水平。IFN-γ在PT第3天恢复至输血前水平，其产生不受AMG处理的影响。另一方面，血清白细胞介素-4（IL-4）在输血前和输血过程中检测不到。在PT第3天，受体脾细胞可以介导体外抗P815（auto）、抗EL 4（allo）和抗R1.1（third-party MHC）细胞毒性，并且这些应答在PT第7天达到最大。同时，受体脾细胞对刀豆球蛋白A（ConA）的体外反应能力显着降低，这是没有看到与脂多糖（LPS）刺激。在PT第3天，在输注小鼠的ConA培养上清液中发现升高的NO2-水平。第5次血小板输注时检测血清抗供者同种抗体。AMG处理受体小鼠显著抑制输血诱导的细胞毒性和ConA刺激的NO2-产生，并恢复ConA诱导的增殖至正常水平。AMG似乎选择性抑制血小板诱导的同种抗体产生，因为它不影响在辅助治疗中通过输注10（6）个同种异体白细胞或通过免疫接种外源蛋白抗原（人丙种球蛋白）诱导的抗体产生。这些结果表明，在体内AMG敏感的机制是必不可少的受体启动体液IgG免疫应答对同种异体血小板。(C)1996年，美国血液学会。
Leukoreduced allogeneic platelet transfusions have been previously shown to initially stimulate an in vitro cellular cytotoxicity and subsequently induce the formation of immunoglobulin G (IgG) antidonor alloantibodies. To further characterize these responses and determine if they are related, recipient BALB/c H-2(d) mice were treated with aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 10(8) C57BL/6 H2(b) platelets. In control, non-AMG-treated mice, transfusion significantly (P < .01) increased serum levels of interferon-gamma (IFN-gamma) by day 1 posttransfusion (PT). IFN-gamma returned to pretransfusion levels by day 3 PT, and its production was not affected by AMG treatment. Serum interleukin-4 (IL-4), on the other hand, was undetectable before and during the transfusion protocol. By day 3 PT, recipient spleen cells could mediate in vitro anti-P815 (auto), anti-EL4 (allo), and anti-R1.1 (third-party MHC) cytotoxicity, and these responses were maximal by day 7 PT. Concurrently, a significant reduction in the in vitro ability of recipient splenocytes to respond to Concanavalin A (ConA) was observed; this was not seen with lipopolysaccharide (LPS) stimulation. Elevated levels of NO2- were found in the ConA culture supernatants from transfused mice at day 3 PT. Serum antidonor alloantibodies were detected by the fifth platelet transfusion. AMG treatment of recipient mice significantly inhibited the transfusion-induced cytotoxicity and ConA-stimulated NO2- production, and restored ConA-induced proliferation to normal levels. AMG appeared to selectively inhibit platelet-induced alloantibody production in that it did not affect antibody production induced by transfusions with 10(6) allogeneic leukocytes or by immunization with a foreign protein antigen, human gamma globulin, in adjuvant therapy. These results indicate that an in vivo AMG-sensitive mechanism is essential for recipients to initiate a humoral IgG immune response against allogeneic platelets. (C) 1996 by The American Society of Hematology.