Budde K, Coleman D L, Lacy J, Sterzel R B
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Am J Physiol. 1989 Dec;257(6 Pt 2):F1065-78. doi: 10.1152/ajprenal.1989.257.6.F1065.
Because inflammatory processes in renal glomeruli may involve monocyte-macrophages (MPs) and T-lymphocytes, we have investigated whether products of glomerular mesangial cells (MCs) can stimulate the proliferative activity of these effector cells. We found that cultured rat MCs (subcultures 2-15), maintained under serum-free conditions, secrete a soluble factor into the supernate [MC-conditioned medium (CM)], which supports growth of the T-helper cell-derived line HT-2. Moreover, MC-CM increased [3H]thymidine incorporation by thioglycollate-elicited peritoneal MPs but did not induce growth of the interleukin 2 (IL-2)- or interleukin 4 (IL-4)-dependent cell line CTLL-2. Further functional, serological, and biochemical analysis of MC-CM revealed that rat MCs secrete a cytokine that, by all of the techniques used, is indistinguishable from granulocyte-macrophage colony-stimulating factor (GM-CSF). Both northern blot and in situ hybridization with a specific cDNA probe for murine GM-CSF showed that MCs express GM-CSF mRNA transcripts. The present findings indicate that cultured rat MCs produce GM-CSF. Release of GM-CSF by MCs in vivo may play a role in the interaction of MCs with MPs, T-cells, and neutrophils in glomerular disease.
由于肾小球中的炎症过程可能涉及单核细胞-巨噬细胞(MPs)和T淋巴细胞,我们研究了肾小球系膜细胞(MCs)的产物是否能刺激这些效应细胞的增殖活性。我们发现,在无血清条件下培养的大鼠MCs(传代培养2 - 15代)会向培养液上清中分泌一种可溶性因子[MC条件培养基(CM)],该因子可支持T辅助细胞系HT - 2的生长。此外,MC - CM增加了巯基乙酸诱导的腹腔MPs对[³H]胸腺嘧啶核苷的掺入,但未诱导白细胞介素2(IL - 2)或白细胞介素4(IL - 4)依赖的细胞系CTLL - 2的生长。对MC - CM进行的进一步功能、血清学和生化分析表明,大鼠MCs分泌一种细胞因子,通过所有使用的技术检测,该细胞因子与粒细胞-巨噬细胞集落刺激因子(GM - CSF)无法区分。用小鼠GM - CSF的特异性cDNA探针进行的Northern印迹和原位杂交均显示,MCs表达GM - CSF mRNA转录本。目前的研究结果表明,培养的大鼠MCs可产生GM - CSF。MCs在体内释放GM - CSF可能在肾小球疾病中MCs与MPs、T细胞和中性粒细胞的相互作用中发挥作用。