生物谷報道：研究人員在2007年1月號的《自然—免疫學》上報告說，他們深入認識了多發(fā)性硬化癥復發(fā)的病理學原理,。研究顯示，血清骨橋蛋白分子是一種炎癥調(diào)節(jié)因子,，能延長自動攻擊免疫細胞的壽命,，從而促進了疾病的進展。
在復發(fā)多發(fā)性硬化癥的模式動物小鼠中,，Larry Steinman和同事研究了一種缺失血清骨橋蛋白的小鼠,，這種小鼠的多發(fā)性硬化癥狀不太嚴重,。與同窩出生的正常小鼠相比，自動攻擊免疫細胞在缺失血清骨橋蛋白分子的小鼠大腦中存活的機會更少,。相反,，獲得血清骨橋蛋白分子的小鼠的疾病更為嚴重，最終導致死亡,。
利用這些信息,，作者發(fā)現(xiàn)，在實驗室中血清蛋白分子增加了自動攻擊免疫細胞的壽命,，改變了調(diào)節(jié)細胞生存和分裂的幾種基因的表達,。他們由此推測，以血清骨橋蛋白為治療靶標也許有助于多發(fā)性硬化癥患者,。
Figure1．Opn induces worsening autoimmune relapses and severe progression of autoimmune demyelinating disease.
(a) Clinical scores of EAE induced by immunization of Opn-wild-type mice (Opn-WT; n = 10) and Opn-knockout mice4 (Opn-KO; n = 14) with MOG peptide; half of the Opn-knockout mice (n = 7) were given rOPN daily for 32 d after the initial peak of the clinical disease, initiated during the first remission of each mouse. (b) Clinical scores of female SJL/J mice immunized with the peptide of proteolipid protein and then treated with PBS (n = 9 mice) or with rOPN (n = 9 mice) as described in a. Upward arrows (a,b), first day of rOpn treatment. (c) Clinical scores of MOG-specific TCR–transgenic mice23 given primary immunization with MOG peptide without pertussis toxin and then treated with PBS (n = 6 mice) or with rOPN (n = 6 mice) daily beginning on the day of primary immunization; mice were immunized with MOG peptide plus pertussis toxin 25 d after primary immunization. (d) Hematoxylin-and-eosin staining of optic nerve tissue sections isolated from MOG-specific TCR–transgenic mice with optic neuritis and EAE. Naive, no MOG immunization. Original magnification, 200. (e) TUNEL staining of brain and spinal cord tissue from Opn-knockout and Opn-wild-type mice immunized with MOG peptide to induce EAE, obtained on day 17 after immunization. Arrows indicate TUNEL-positive (brown) nuclei of infiltrating lymphocytes stained with 3,3'-diaminobenzidine. Scale bars, 25 m. Data represent mean clinical score (+ s.e.m.) of three experiments (a–c) and images are of representative tissues from three (d) or two (e) experiments.
原文出處：
Nature Immunology January 2007, Volume 8 No 1
Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells pp74 - 83
Eun Mi Hur, Sawsan Youssef, M Edward Haws, Susan Y Zhang, Raymond A Sobel & Lawrence Steinman
Published online: 03 December 2006 | doi:10.1038/ni1415
Abstract | Full text | PDF (506K) | Supplementary Information
See also: News and Views by Stromnes & Goverman
相關(guān)基因：
SPP1
Official Symbol: SPP1 and Name: secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) [Homo sapiens]
Other Aliases: BNSP, BSPI, ETA-1, MGC110940, OPN
Other Designations: SPP1/CALPHA1 fusion; osteopontin; osteopontin/immunoglobulin alpha 1 heavy chain constant region fusion protein; secreted phosphoprotein 1; secreted phosphoprotein-1 (osteopontin, bone sialoprotein)
Chromosome: 4; Location: 4q21-q25
MIM: 166490
GeneID: 6696
背景知識：
多發(fā)性硬化癥是一種中樞神經(jīng)系統(tǒng)的疾病,，也就是說它的病變位于腦部或脊髓。我們的神經(jīng)細胞有許多樹枝狀的神經(jīng)纖維,，這些纖維就像錯縱復雜的電線一般,，在我們的中樞神經(jīng)系統(tǒng)中組織成綿密復雜的網(wǎng)絡(luò)。大自然很巧妙的在我們神經(jīng)纖維的外面包裹著一層叫“髓鞘”的物質(zhì),，髓鞘不僅像電線的塑料皮一樣讓不同的電線不致短路,，同時人體的髓鞘還可以加速我們神經(jīng)訊號的傳導?！ ?
當這些髓鞘被破壞后,，我們神經(jīng)訊號的傳導就會變慢甚至停止。多發(fā)性硬化癥就是因為在中樞神經(jīng)系統(tǒng)中產(chǎn)生大小不一的塊狀髓鞘脫失而產(chǎn)生癥狀,。所謂“硬化”指的是這些髓鞘脫失的區(qū)域因為組織修復的過程中產(chǎn)生的疤痕組織而變硬,。這些硬塊可能會有好幾個，隨著時間的進展,，新的硬塊也可能出現(xiàn),，所以稱作“多發(fā)性”。
骨橋蛋白Opn是一個廣泛表達的多效性細胞因子（pleiotropic cytokine）,，在炎癥發(fā)生時會提高表達水平,。它在細胞中可以有很多不同的同源異型蛋白（isoform）,，這是由不同的剪接方式,，轉(zhuǎn)錄后磷酸化、糖基化修飾,，以及凝血酶（Thrombin）的酶解造成的結(jié)果,。Opn參與很多生物學過程，包括骨重建,，炎癥,，癌癥和對感染病的免疫等,。這些多功能的生物學活性也反映出了該蛋白于細胞外可以結(jié)合多種不同的整聯(lián)蛋白受體（integrin receptor）和CD44異變體的本領(lǐng)，于細胞內(nèi)可以與信號轉(zhuǎn)導分子相互作用的本領(lǐng),。
