Rosenberg N L, Ringel S P, Kotzin B L
Department of Neurology, V.A. Medical Centre, Denver, Colorado 80220.
Clin Exp Immunol. 1987 Apr;68(1):117-29.
Experimental autoimmune myositis (EAM), was produced in SJL/J mice by injection of an emulsion of crude syngeneic muscle homogenate and complete Freund's adjuvant (CFA). Nearly all injected SJL/J mice showed necrotic muscle fibres associated with infiltrating mononuclear cells, both within the necrotic fibres and in surrounding endomysial connective tissue. The disease in SJL/J mice was confined to skeletal muscle. Eight other mouse strains of different major histocompatibility types, similarly injected, failed to develop EAM. Direct immunofluorescence staining revealed prominent IgG deposition at the muscle cell membrane and in perimysial and endomysial connective tissue. This staining was present in both involved muscle of immunized SJL/J mice as well as in undamaged muscle from other immunized strains. Circulating anti-muscle antibodies as detected by indirect immunofluorescence staining of normal muscle were also present in both SJL/J mice and non-susceptible strains. An enzyme-linked immunosorbent assay (ELISA) was also developed for detection of serum anti-muscle antibody activity. Three strains of mice, including SJL/J, failed to develop significantly elevated anti-muscle antibody activity after injection of muscle and CFA, whereas six other strains that did not demonstrate histological myositis developed a 10- to 20-fold elevation of anti-muscle antibody activity. These results suggest that the ability to produce anti-muscle antibodies after immunization does not determine susceptibility to histological disease. Although EAM has been previously induced in other species, there have not been previous descriptions of this experimental disease in mice. This murine model may provide new insight into the immunopathogenesis of human inflammatory myopathies.
通过注射同基因粗制肌肉匀浆与完全弗氏佐剂(CFA)的乳剂,在SJL/J小鼠中诱发实验性自身免疫性肌炎(EAM)。几乎所有注射的SJL/J小鼠都出现了坏死的肌纤维,伴有浸润的单核细胞,这些细胞既存在于坏死纤维内,也存在于周围的肌内膜结缔组织中。SJL/J小鼠的疾病局限于骨骼肌。对其他8种不同主要组织相容性类型的小鼠品系进行类似注射后,未能诱发EAM。直接免疫荧光染色显示,在肌细胞膜以及肌束膜和肌内膜结缔组织中有明显的IgG沉积。这种染色在免疫的SJL/J小鼠的受累肌肉以及其他免疫品系的未受损肌肉中均有出现。通过对正常肌肉进行间接免疫荧光染色检测到的循环抗肌肉抗体,在SJL/J小鼠和非易感品系中也都存在。还开发了一种酶联免疫吸附测定(ELISA)法来检测血清抗肌肉抗体活性。包括SJL/J在内的3种小鼠品系在注射肌肉和CFA后,抗肌肉抗体活性未显著升高,而其他6种未表现出组织学肌炎的品系,其抗肌肉抗体活性升高了10至20倍。这些结果表明,免疫后产生抗肌肉抗体的能力并不能决定对组织学疾病的易感性。虽然此前已在其他物种中诱发了EAM,但此前尚未有关于小鼠这种实验性疾病的描述。这种小鼠模型可能会为人类炎性肌病的免疫发病机制提供新的见解。