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豚鼠对实验性自身免疫性脑脊髓炎和神经炎的易感性及抗性与促凝血和抗凝血活性的诱导相关。

Susceptibility and resistance to experimental autoimmune encephalomyelitis and neuritis in the guinea pig correlate with the induction of procoagulant and anticoagulant activities.

作者信息

Geczy C L, Roberts I M, Meyer P, Bernard C C

出版信息

J Immunol. 1984 Dec;133(6):3026-36.

PMID:6208270
Abstract

Activation of macrophage procoagulant activity (MPCA) is involved in the manifestation of EAE and EAN in susceptible guinea pigs and provides a mechanism for the deposition of fibrin, which is a feature of histologic lesions of EAE. Peritoneal exudate cells (PEC) from susceptible (strain 13) guinea pigs immunized with either central or peripheral nervous tissue antigens produce procoagulant activity when incubated with the immunogen in vitro. The production of the procoagulant is quantitative and antigen-specific and is maximal at the time of clinical signs of the disease. After recovery, the production of procoagulant activity decreased. The MPCA test was able to discriminate the biochemical differences existing between chicken and mammalian peripheral nerve proteins, thus providing a quantitative and sensitive indicator of cell-mediated immunity in EAE and EAN. The autoimmune response to brain and nerve antigens in nonsusceptible (strain 2) guinea pigs was coincident with the antigen-specific production of a cell-bound anticoagulant activity by stimulated mononuclear cells. The production of anticoagulant activity followed the same sequence of time changes after immunization as that of the MPCA in susceptible guinea pigs, and high immunizing doses of nerve antigens induced high levels of anticoagulant activity. The same cells produced high levels of procoagulant when incubated with tuberculin or lipopolysaccharide. The recalcification time of normal plasma was prolonged by the anticoagulant, and the decreased clotting time of plasma induced by the procoagulant activity obtained by incubating sensitized strain 13 PEC with myelin basic protein was suppressed by the anticoagulant produced by culturing sensitized strain 2 PEC with myelin basic protein. Preliminary evidence indicates that the anticoagulant has properties similar to antithrombin III. The anticoagulant could play a role in the control of effector cell function, and therefore in recovery from clinical features of EAE and EAN in susceptible guinea pigs.

摘要

巨噬细胞促凝活性(MPCA)的激活参与了易感豚鼠实验性自身免疫性脑脊髓炎(EAE)和实验性变态反应性神经炎(EAN)的表现,并为纤维蛋白沉积提供了一种机制,这是EAE组织学损伤的一个特征。用中枢或周围神经组织抗原免疫的易感(13品系)豚鼠的腹腔渗出细胞(PEC)在体外与免疫原孵育时会产生促凝活性。促凝剂的产生是定量的且具有抗原特异性,在疾病临床症状出现时达到最大值。恢复后,促凝活性的产生减少。MPCA试验能够区分鸡和哺乳动物周围神经蛋白之间存在的生化差异,从而为EAE和EAN中细胞介导的免疫提供了一个定量且敏感的指标。非易感(2品系)豚鼠对脑和神经抗原的自身免疫反应与受刺激的单核细胞产生细胞结合抗凝活性的抗原特异性相关。抗凝活性的产生在免疫后遵循与易感豚鼠中MPCA相同时间变化顺序,高剂量的神经抗原免疫诱导高水平的抗凝活性。当与结核菌素或脂多糖孵育时,相同的细胞会产生高水平的促凝剂。抗凝剂延长了正常血浆的复钙时间,而用髓鞘碱性蛋白孵育致敏的13品系PEC所获得的促凝活性诱导的血浆凝血时间缩短被用髓鞘碱性蛋白培养致敏的2品系PEC所产生的抗凝剂所抑制。初步证据表明该抗凝剂具有类似于抗凝血酶III的特性。该抗凝剂可能在效应细胞功能的控制中发挥作用,因此在易感豚鼠从EAE和EAN的临床特征中恢复方面发挥作用。

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