Gressner A M
Department of Clinical Chemistry, Philipps University, Marburg, Germany.
J Hepatol. 1995;22(2 Suppl):28-36.
Based on current knowledge a "3-step cascade model of fat-storing cell activation" is suggested, which implies sequential cross-talk between fat-storing cells, hepatocytes, Kupffer cells, thrombocytes, endothelial cells, and myofibroblasts (transformed fat-storing cells) (Fig. 4). In a preinflammatory phase (I) due to membrane damage (often the initiating event) release of a paracrine acting mitogen from hepatocytes is favoured, which initiates proliferation of fat-storing cells. During the subsequent inflammatory phase (II) cytokines of activated Kupffer cells/macrophages (TGF-beta, TGF-alpha, "lipocyte activating factor" etc.) and of disintegrated platelets (TGF-beta, EGF-like factors, PDGF etc.) are released at the locus of necrosis. TGF-beta, the prototype of a fibrogenic cytokine (102), markedly affects the transformation of fat-storing cells to myofibroblasts. The latter cell type is stimulated during the postinflammatory phase (III) via an autocrine loop by TGF-alpha, TGF-beta, and FGF. In combination with further paracrine stimulation of untransformed fat-storing cells by myofibroblasts the postinflammatory phase potentially contributes to self-perpetuation of fibrogenesis even after cessation of the initiating event (43). In addition to polypeptide mediators, low molecular weight chemical compounds like acetaldehyde, reactive oxygen species, eicosanoids, and lactate are potentially involved in fat-storing cell activation (26). In the network of cytokines, extracellular matrix, and cells several positively and negatively acting regulatory loops are possible.
基于目前的知识，有人提出了一种“贮脂细胞激活的三步级联模型”，这意味着贮脂细胞、肝细胞、库普弗细胞、血小板、内皮细胞和成肌纤维细胞（转化的贮脂细胞）之间存在顺序性的相互作用（图4）。在炎症前期（I），由于膜损伤（通常是起始事件），肝细胞会释放一种旁分泌作用的促有丝分裂原，从而引发贮脂细胞的增殖。在随后的炎症期（II），活化的库普弗细胞/巨噬细胞（转化生长因子-β、转化生长因子-α、“脂肪细胞激活因子”等）以及解体的血小板（转化生长因子-β、表皮生长因子样因子、血小板衍生生长因子等）释放的细胞因子会在坏死部位出现。转化生长因子-β是一种促纤维化细胞因子的原型（102），它会显著影响贮脂细胞向肌成纤维细胞的转化。在炎症后期（III），肌成纤维细胞通过自分泌环受到转化生长因子-α、转化生长因子-β和碱性成纤维细胞生长因子的刺激。在肌成纤维细胞对未转化的贮脂细胞的进一步旁分泌刺激作用下，炎症后期甚至在起始事件停止后仍可能导致纤维化的自我延续（43）。除了多肽介质外，低分子量化合物如乙醛、活性氧、类花生酸和乳酸也可能参与贮脂细胞的激活（26）。在细胞因子网络、细胞外基质和细胞中，可能存在多个正负作用的调节环。
