生物谷報道：研究人員在2007年1月號的《自然—免疫學(xué)》上報告說,，他們深入認(rèn)識了多發(fā)性硬化癥復(fù)發(fā)的病理學(xué)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(xì)胞的壽命，從而促進(jìn)了疾病的進(jìn)展。
在復(fù)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(yán)重。與同窩出生的正常小鼠相比,，自動攻擊免疫細(xì)胞在缺失血清骨橋蛋白分子的小鼠大腦中存活的機(jī)會更少,。相反，獲得血清骨橋蛋白分子的小鼠的疾病更為嚴(yán)重,，最終導(dǎo)致死亡,。
利用這些信息，作者發(fā)現(xiàn),，在實(shí)驗(yàn)室中血清蛋白分子增加了自動攻擊免疫細(xì)胞的壽命，改變了調(diào)節(jié)細(xì)胞生存和分裂的幾種基因的表達(dá),。他們由此推測,，以血清骨橋蛋白為治療靶標(biāo)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(xì)胞有許多樹枝狀的神經(jīng)纖維，這些纖維就像錯縱復(fù)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(fù)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(dǎo),。
當(dāng)這些髓鞘被破壞后,，我們神經(jīng)訊號的傳導(dǎo)就會變慢甚至停止,。多發(fā)性硬化癥就是因?yàn)樵谥袠猩窠?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?yàn)榻M織修復(fù)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(jìn)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(dá)的多效性細(xì)胞因子（pleiotropic cytokine），在炎癥發(fā)生時會提高表達(dá)水平,。它在細(xì)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(xué)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(xué)活性也反映出了該蛋白于細(xì)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(xì)胞內(nèi)可以與信號轉(zhuǎn)導(dǎo)分子相互作用的本領(lǐng),。
