Jarvis M, Marzolini M, Wang X N, Jackson G, Sviland L, Dickinson A M
University Department of Haematology, Royal Victoria Infirmary, Newcastle Upon Tyne, UK.
Transplantation. 2003 Sep 15;76(5):849-53. doi: 10.1097/01.TP.0000083556.73555.78.
The heat shock proteins are increasingly becoming associated with immunopathologic phenomena, being induced in response to inflammation. They are highly immunogenic and are postulated as playing a role in both innate and adaptive immunity. Their proposed role in peptide binding and antigen presentation could suggest a potential role in the alloreactive process that leads to graft-versus-host disease (GVHD) after bone marrow transplantation.
In this study we examined the expression of the widely studied heat shock protein 70 (hsp70) in an in vitro-generated graft-versus-host reaction in human skin, using streptavidin biotin immunohistochemistry and laser scanning confocal microscopy.
Hsp70 expression was correlated with high graft-versus-host responses (P<0.001) and was confirmed using laser scanning confocal microscopy. Increased expression of hsp70 was further defined due to increases in the inducible form of hsp70. Expression of inducible hsp70 was predictive of both clinical acute GVHD (P=0.001) and incidence of chronic GVHD (P<0.001).
This investigation has demonstrated for the first time the expression of hsp70 in a human model of GVHD, suggesting involvement in the pathogenesis of the disease and providing the basis for further investigation. Increased expression of inducible hsp70 in the model could provide a biologic marker for the prediction of clinical acute and chronic GVHD.
热休克蛋白越来越多地与免疫病理现象相关联，它是在炎症反应中被诱导产生的。它们具有高度免疫原性，并被假定在固有免疫和适应性免疫中均发挥作用。它们在肽结合和抗原呈递方面的假定作用可能提示其在导致骨髓移植后移植物抗宿主病（GVHD）的同种异体反应过程中具有潜在作用。
在本研究中，我们使用链霉亲和素生物素免疫组织化学和激光扫描共聚焦显微镜，检测了广泛研究的热休克蛋白70（hsp70）在人皮肤体外产生的移植物抗宿主反应中的表达。
hsp70表达与高移植物抗宿主反应相关（P<0.001），并通过激光扫描共聚焦显微镜得到证实。hsp70表达增加是由于hsp70可诱导形式的增加所致。可诱导hsp70的表达可预测临床急性GVHD（P=0.001）和慢性GVHD的发生率（P<0.001）。
本研究首次证明了hsp70在GVHD人类模型中的表达，提示其参与了该疾病的发病机制，并为进一步研究提供了基础。模型中可诱导hsp70表达的增加可为预测临床急性和慢性GVHD提供生物学标志物。
