Increased calpain expression in activated glial and inflammatory cells in experimental allergic encephalomyelitis
Increased calpain expression in activated glial and inflammatory cells in experimental allergic encephalomyelitis
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DOI：
10.1073/pnas.95.10.5768
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发表时间：
1998-05-12
影响因子：
11.1
通讯作者：
Banik, NL
中科院分区：
文献类型：
--
作者：
Shields, DC;Tyor, WR;Banik, NL
在脱髓鞘疾病（如多发性硬化症（MS））中，髓鞘膜结构由于髓鞘蛋白丢失而不稳定。钙激活中性蛋白酶（calpain）被认为参与髓鞘蛋白降解，因为已知的calpain底物[髓鞘碱性蛋白（MBP）;在探索钙蛋白酶在脱髓鞘疾病中的作用时，我们检测了患有急性实验性变态反应性脑脊髓炎（EAE）的刘易斯大鼠中的钙蛋白酶表达，使用双重免疫荧光标记来鉴定表达钙蛋白酶的细胞，我们用多克隆millicalpain抗体标记大鼠脊髓切片中的钙蛋白酶，用单克隆抗体标记神经胶质细胞。（GFAP、0X 42、GalC）和炎性（CD 2、ED 2、干扰素γ）细胞特异性标志物。与对照组相比，激活的小胶质细胞（OX 42）和浸润性巨噬细胞（ED 2）中钙蛋白酶表达增加，少突胶质细胞（半乳糖苷）和星形胶质细胞（GP;AP）在正常脊髓中具有组成性钙蛋白酶表达，而与佐剂对照组中的星形胶质细胞相比，EAE动物脊髓中的反应性星形胶质细胞表现出显著增加的钙蛋白酶水平。EAE大鼠脊髓中的少突胶质细胞在某些区域表达钙蛋白酶水平增加，但总体上钙蛋白酶表达的增加很小。4级EAE中大多数T细胞表达低水平的钙蛋白酶，但干扰素γ阳性细胞表现出明显增加的钙蛋白酶表达。这些发现表明，在EAE中激活的神经胶质细胞和炎症细胞中钙蛋白酶水平的增加可能有助于脱髓鞘疾病如MS中髓鞘的破坏。
In demyelinating diseases suck as multiple sclerosis (MS), myelin membrane structure is destabilized as myelin proteins are lost. Calcium-activated neutral proteinase (calpain) is believed to participate in myelin protein degradation because known calpain substrates [myelin basic protein (MBP); myelin-associated glycoprotein] are degraded in this disease, In exploring the role of calpain in demyelinating diseases, we examined calpain expression in Lewis rats with acute experimental allergic encephalomyelitis (EAE), an animal model for MS. Using double-immunofluorescence labeling to identify cells expressing calpain, we labeled rat spinal cord sections for calpain with a polyclonal millicalpain antibody and with mAbs for glial (GFAP, OX42, GalC) and inflammatory (CD2, ED2, interferon gamma) cell-specific markers. Calpain expression was increased in activated microglia (OX42) and infiltrating macrophages (ED2) compared with controls, Oligodendrocytes (galactocerebroside) and astrocytes (GP;AP) had constitutive calpain expression in normal spinal cords whereas reactive astrocytes in spinal cords from animals with EAE exhibited markedly increased calpain levels compared with astrocytes in adjuvant controls. Oligodendrocytes in spinal cords from rats with EAE expressed increased calpain levels in some areas, but overall the increases in calpain expression were small. Most T cells in grade 4 EAE expressed low levels of calpain, but interferon gamma-positive cells demonstrated markedly increased calpain expression. These findings suggest that increased levels of calpain in activated glial and inflammatory cells in EAE may contribute to myelin destruction in demyelinating diseases such as MS.