謝松洲2006-07-262018-07-112006-07-262018-07-112005http://ntur.lib.ntu.edu.tw//handle/246246/23693Granular proteins of neutrophil have long been recognized as mediators of innate host defense. Newly discovered evidence suggests that granular constituents may also participate in adaptive immune response. Cathepsin G (CG) is a highly cationic serine proteinase contained in the azurophilic granules of human polymorphonuclear neutrophils (PMN). A number of in vitro studies have revealed diverse putative functions of cathepsin G extracellularly including: (1) antimicrobial activity (2) regulation of inflammatory responses (3) degradation of extracellular matrix and (4) vasoregulation. However, its effect on immunological functions of PMN and mononuclear cells (MNC) have been rarely reported in the literature. We use MTT test, RT-PCR, flow cytometry, ELISA and Western blot to investigate the effects of cathepsin G on immunological functions of PMN and MNC. We found that cathepsin G from 5 to 100 mU/ml did not affect the survival of PMN and MNC but effectively inhibit the phagocytosis of PMN. In addition, cathepsin G did not change the mRNA expression of inflammatory cytokines such as IL-1 β , IL-4, IL-8, IL-10 and TNF-α in PMN. However, the expression of IL-2 and TNF-α mRNA was suppressed by CG. At the same time, cathepsin G enhanced the IL-8 production of PMN and MNC. The soluble IL-2 receptor of MNC was also increased by presence of CG. It is conceivable that IL-8 derived from macrophage facilitates PMN chemotaxis and activation. The increased release of soluble IL-2 receptor of T lymphocyte represents an activation marker of T lymphocyte. Moreover, cathepsin G could modulate cationic ion channel expression on the cell surface. CG increased the Na+-K+-ATPase expression on the surface of PMN and MNC but suppressed renal outer medulary K+ channel (ROMK1) and modestly increased epithelial sodium channel (ENaC) expression in PMN. But the reverse finding in MNC was noted. These results indicate CG exerts the immune regulation on PMN and MNC via the biologically functional modulation. In addition to the protease activity, CG plays a critical role in the adaptive immunity.application/pdf414838 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23693/1/932314B002088.pdf