NORMAL AND PATHOLOGIC MECHANISMS OF INFLAMMATION AND REPAIR

宿主对病原体和其他抗原的防御依赖于单核细胞 细胞招募，激活，最后，下调。这项研究 该项目的重点是描绘细胞和分子机制 控制这些事件。而单核细胞很容易对 炎性趋化刺激，来自内部的单核巨噬细胞 炎症部位表现出缺陷的趋化活性，原因是失去 趋化配体(C5a)受体。单核细胞成熟度增加 表现为人类白细胞抗原DR的增加被发现与减少相关 趋化受体的表达为巨噬细胞提供机制 炎症部位的堆积。一旦在炎症性疾病中 诱导巨噬细胞表达CD16(Fc-GammaR111) 炎性细胞因子，转化生长因子-β。通过该受体的信号转导 调节免疫吞噬作用，并可通过 释放活性氧中间体(ROI)。转化生长因子-β的能力 刺激单核细胞表型和功能改变是短暂的，因为 转化生长因子-β受体在分化过程中丢失。其他机制 可能通过释放IL-4而发生免疫抑制，IL-4可以 抑制转化生长因子-β诱导的Fc-GammaR111表达，抑制ROI，以及 抑制单核细胞的生产。因此，免疫细胞衍生的细胞因子 提供一系列细胞间信号，这些信号启动、增强和 最终，抑制免疫反应。

Host defense to pathogens and other antigens is dependent upon mononuclear cell recruitment, activation and finally, downregulation. This research project focuses on delineating the cellular and molecular mechanisms controlling these events. Whereas blood monocytes readily respond to inflammatory chemotactic stimuli, mononuclear phagocytes from within inflammatory sites exhibit defective chemotactic activity due to loss of chemotactic ligand (C5a) receptors. Increased monocyte maturation as reflected by increased HLA-DR was found to be associated with decreased chemotaxis receptor expression providing a mechanism for macrophage accumulation within an inflammatory site. Once within the inflammatory site, macrophages are induced to express CD16 (Fc gammaR111) by the inflammatory cytokine, TGF-beta. Signal transduction through this receptor regulates immunophagocytosis and can promote tissue destruction through the release of reactive oxygen intermediates (ROI). The ability of TGF-beta to stimulate monocyte phenotypic and functional changes is transient since TGF-beta receptors are lost during differentiation. Additional mechanisms of immune suppression may occur through the release of IL-4 which can suppress TGF-beta-induced Fc gammaR111 expression, inhibit ROI, and downregulate monokine production. Thus, immune cell-derived cytokines provide a series of intercellular signals which initiate, augment and ultimately, suppress the immune response.