Bacher M, Meinhardt A, Lan H Y, Mu W, Metz C N, Chesney J A, Calandra T, Gemsa D, Donnelly T, Atkins R C, Bucala R
Picower Institute for Medical Research, Manhasset, New York 10021, USA.
Am J Pathol. 1997 Jan;150(1):235-46.
Macrophage migration inhibitory factor (MIF) is an important constituent of the host response to stress and infection and is the first mediator that has been identified to be released from immune cells upon stimulation with glucocorticoids. MIF also has been shown to be secreted from the anterior pituitary gland, monocytes/macrophages, and T cells activated by various proinflammatory stimuli. Once released, MIF acts to counter-regulate the inhibitory effect of glucocorticoids on inflammatory cytokine production. To characterize more precisely the role of MIF in the host response to infection, we undertook a systematic analysis of MIF expression in various organs of the rat after endotoxin (lipopolysaccharide) administration. MIF protein and mRNA were analyzed by immunohistochemistry and in situ hybridization, respectively. MIF was found to be expressed constitutively in organs such as the lung, liver, kidney, spleen, adrenal gland, and skin. Significant quantities of MIF protein were detected preformed in various cell types and appeared to be released as a consequence of endotoxemia. In virtually all tissues examined, the loss of MIF protein 6 hours after lipopolysaccharide administration was accompanied by the induction of MIF mRNA and, at 24 hours, by the restoration of immunoreactive, intracellular MIF. The constitutive production of MIF by several cell and tissue types together with its rapid release from intracellular pools distinguishes MIF from other cytokines or hormonal mediators and significantly expands the physiological role of this unique counter-regulator of glucocorticoid action.
巨噬细胞移动抑制因子（MIF）是宿主对应激和感染反应的重要组成部分，是首个被确定在糖皮质激素刺激下从免疫细胞释放的介质。MIF也已被证明可从前脑垂体、单核细胞/巨噬细胞以及受到各种促炎刺激而活化的T细胞中分泌。一旦释放，MIF就会发挥作用，对抗糖皮质激素对炎性细胞因子产生的抑制作用。为了更精确地表征MIF在宿主感染反应中的作用，我们对内毒素（脂多糖）给药后大鼠各器官中MIF的表达进行了系统分析。分别通过免疫组织化学和原位杂交分析MIF蛋白和mRNA。发现MIF在肺、肝、肾、脾、肾上腺和皮肤等器官中组成性表达。在各种细胞类型中检测到大量预先形成的MIF蛋白，并且似乎是内毒素血症的结果而释放。在几乎所有检查的组织中，脂多糖给药6小时后MIF蛋白的减少伴随着MIF mRNA的诱导，并且在24小时时伴随着免疫反应性细胞内MIF的恢复。几种细胞和组织类型对MIF的组成性产生及其从细胞内池的快速释放，将MIF与其他细胞因子或激素介质区分开来，并显著扩展了这种独特的糖皮质激素作用反向调节因子的生理作用。
