Kovacs E J, Van Stedum S, Neuman J E
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Stritch School of Medicine, Maywood, IL.
Immunobiology. 1994 Apr;190(3):263-74. doi: 10.1016/S0171-2985(11)80274-3.
We have previously reported that culture of human peripheral blood leukocytes with interleukin-2 (IL-2) triggers the secretion of mediators which induce fibroblast proliferation and collagen synthesis. In addition, fibrogenic cytokines (transforming growth factor-beta 1 (TGF beta 1) and platelet-derived growth factor (PDGF) A and B chain) are present in the peritoneal fluid of patients undergoing intraperitoneal immunotherapy (IL-2-activated killer cells and IL-2) who go on to develop peritoneal adhesions. To determine the role of IL-2 in the formation of these adhesions, we chose to investigate whether IL-2 can induce the expression of fibrogenic cytokine genes in resident rat peritoneal macrophages. Cells were cultured with or without IL-2 or lipopolysaccharide (LPS) and expression of PDGF A chain, PDGF B chain, and TGF beta 1 mRNAs was determined. PDGF A and B chain mRNAs are minimally expressed in macrophages prior to stimulation and are induced within 2 hours of treatment with IL-2. In contrast, TGF beta 1 mRNA is constitutively expressed and can not be upregulated. The studies suggest that peritoneal macrophage-derived PDGF plays a critical role in the production of adhesions in patients receiving intra-abdominal immunotherapy.
我们之前曾报道，用人白细胞介素-2（IL-2）培养人外周血白细胞会触发介质的分泌，这些介质可诱导成纤维细胞增殖和胶原蛋白合成。此外，在接受腹腔内免疫疗法（IL-2激活的杀伤细胞和IL-2）并继而发生腹膜粘连的患者的腹腔液中存在促纤维化细胞因子（转化生长因子-β1（TGF-β1）以及血小板衍生生长因子（PDGF）A链和B链）。为了确定IL-2在这些粘连形成中的作用，我们选择研究IL-2是否能诱导大鼠腹腔常驻巨噬细胞中促纤维化细胞因子基因的表达。将细胞在有或无IL-2或脂多糖（LPS）的情况下进行培养，并测定PDGF A链、PDGF B链和TGF-β1 mRNA的表达。在刺激前，PDGF A链和B链mRNA在巨噬细胞中的表达极低，在用IL-2处理后2小时内被诱导表达。相比之下，TGF-β1 mRNA是组成性表达的，且不能被上调。这些研究表明，腹腔巨噬细胞衍生的PDGF在接受腹腔内免疫疗法的患者粘连形成过程中起关键作用。
