Knudsen Eirunn, Iversen Per Ole, Van Rooijen Nico, Benestad Haakon Breien
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway.
Eur J Haematol. 2002 Nov-Dec;69(5-6):284-96. doi: 10.1034/j.1600-0609.2002.02657.x.
Pro-inflammatory cytokines attract leukocytes to inflamed tissues and activate them. Few attempts have been made to identify the sources of cytokines in vivo. We examined the importance of peritoneal macrophages in the mobilization and homing of neutrophils to a sterile peritonitis in the rat, with emphasis on their cytokine production. Macrophages, present in virtually all tissues, are known to be easily activated and to serve as an important source of cytokines. Flow cytometric analysis of cells stained intracellularly with tagged antibodies against various cytokines revealed that the peritoneal macrophages were stimulated to produce the following cytokines: interleukin (IL)-1beta, macrophage inflammatory protein-2 (MIP-2), and keratinocyte-derived cytokine (KC). High numbers of neutrophils, activated on arrival into the peritoneal cavity, also produced IL-1beta, whereas lower numbers contained interleukin-6, tumor necrosis factor-alpha, MIP-2, KC, and MIP-1alpha. This marked activation of peritoneal neutrophils was also reflected by increased surface expression of CD11b. On the other hand, peritoneal macrophages expressed high basal levels of CD11b, which were reduced 24 h after the onset of inflammation. In rats selectively depleted of macrophages by i.p. injection of liposome-containing clodronate, the massive influx of neutrophils to the peritoneal cavity was markedly reduced, as was the rapid mobilization of mature bone marrow neutrophils. Local macrophages are important both for the accumulation of neutrophils in the inflamed peritoneal cavity and for the early mobilization of neutrophils from the bone marrow. Macrophage-derived IL-1beta, MIP-2, and KC are possible mediators of neutrophil homing to inflamed tissues.
促炎细胞因子可将白细胞吸引至炎症组织并激活它们。目前鲜有人尝试在体内鉴定细胞因子的来源。我们研究了腹膜巨噬细胞在大鼠无菌性腹膜炎中对中性粒细胞的动员和归巢的重要性，重点关注其细胞因子的产生。巨噬细胞几乎存在于所有组织中，已知其易于被激活并作为细胞因子的重要来源。用针对各种细胞因子的标记抗体进行细胞内染色的流式细胞术分析显示，腹膜巨噬细胞被刺激产生以下细胞因子：白细胞介素（IL）-1β、巨噬细胞炎性蛋白-2（MIP-2）和角质形成细胞衍生细胞因子（KC）。大量在进入腹腔后被激活的中性粒细胞也产生IL-1β，而较少数量的中性粒细胞含有白细胞介素-6、肿瘤坏死因子-α、MIP-2、KC和MIP-1α。腹膜中性粒细胞的这种显著激活也通过CD11b表面表达的增加得以体现。另一方面，腹膜巨噬细胞表达高水平的基础CD11b，在炎症发作后24小时降低。在通过腹腔注射含氯膦酸盐的脂质体选择性清除巨噬细胞的大鼠中，中性粒细胞向腹腔的大量涌入明显减少，成熟骨髓中性粒细胞的快速动员也减少。局部巨噬细胞对于中性粒细胞在炎症腹膜腔中的积聚以及中性粒细胞从骨髓的早期动员都很重要。巨噬细胞衍生的IL-1β、MIP-2和KC可能是中性粒细胞归巢至炎症组织的介质。
