Burr A W, Carpenter M R, Hines J E, Gullick W J, Burt A D
Division of Pathology, School of Pathological Sciences, University of Newcastle upon Tyne, U.K.
J Pathol. 1993 May;170(1):95-100. doi: 10.1002/path.1711700115.
The distribution of transforming growth factor-alpha (TGF alpha) in rat liver during regeneration was studied immunohistochemically using two antibodies, one a polyclonal (26T) raised against a synthetic peptide corresponding to the 17 C-terminal amino acids of the mature rat protein, and the other a monoclonal (Ab-2) raised against recombinant human protein. In normal liver, immunoreactive TGF alpha was detected in perivenular hepatocytes using both antibodies. No sinusoidal cells were found to contain the peptide. In response to carbon tetrachloride (CCI4)-induced necrosis, an initial increase in the intensity of immunoreactivity was noted at 24 h following exposure to the toxin. This coincided with the period immediately preceding the peak of hepatocyte proliferation; Ab-2 immunoreactive cells outnumbered 26T-positive cells. Thereafter there was a reduction in the number of TGF alpha-positive cells, but by day 4 the level of immunoreactivity had returned to that of normal liver. Using bromodeoxyuridine labelling, spatial and temporal relationships between TGF alpha expression and cell proliferation were identified, supporting the concept that this peptide plays an important role in the in vivo regenerative response to hepatic injury via an autocrine mechanism.
利用两种抗体通过免疫组织化学方法研究了再生过程中大鼠肝脏中转化生长因子-α（TGFα）的分布。一种是针对与成熟大鼠蛋白17个C末端氨基酸对应的合成肽产生的多克隆抗体（26T），另一种是针对重组人蛋白产生的单克隆抗体（Ab-2）。在正常肝脏中，使用两种抗体均在肝小叶中央静脉周围的肝细胞中检测到免疫反应性TGFα。未发现窦状隙细胞含有该肽。在四氯化碳（CCl4）诱导的坏死反应中，接触毒素后24小时免疫反应强度开始增加。这与紧接肝细胞增殖高峰之前的时期一致；Ab-2免疫反应性细胞数量超过26T阳性细胞。此后，TGFα阳性细胞数量减少，但到第4天时，免疫反应水平已恢复到正常肝脏水平。使用溴脱氧尿苷标记，确定了TGFα表达与细胞增殖之间的时空关系，支持了该肽通过自分泌机制在体内对肝损伤的再生反应中起重要作用的观点。
