Lira S A, Zalamea P, Heinrich J N, Fuentes M E, Carrasco D, Lewin A C, Barton D S, Durham S, Bravo R
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
J Exp Med. 1994 Dec 1;180(6):2039-48. doi: 10.1084/jem.180.6.2039.
Transgenic mice expressing the chemokine N51/KC in thymus, skin, and tongue showed a marked infiltration of a single class of inflammatory cells (neutrophils) in the sites of transgene expression. In the thymus, neutrophils were most numerous in the cortex and juxta-medullary regions, often forming aggregates or clusters. A similar, but less intense, neutrophilic infiltrate occurred in close proximity to the epidermal basal layer of the tongue and skin. No morphologic evidence of injury was observed in the thymus, skin, or tongue of these transgenic mice, indicating that N51/KC expression induces recruitment but not inflammatory activation of neutrophils. The lack of activation in the thymus resulted in a large senescent neutrophilic population that was phagocytosed by thymic macrophages and epithelial-reticular cells. These results indicate that N51/KC is a neutrophil chemoattractant in vivo and establish these transgenic mice as effective models to study the phenomena of recruitment and clearance of neutrophils, events that are critical for the initiation and resolution of the inflammatory response.
在胸腺、皮肤和舌头中表达趋化因子N51/KC的转基因小鼠,在转基因表达部位出现了单一类型炎症细胞(中性粒细胞)的显著浸润。在胸腺中,中性粒细胞在皮质和近髓质区域数量最多,常形成聚集物或簇。在舌头和皮肤的表皮基底层附近也出现了类似但程度较轻的嗜中性粒细胞浸润。在这些转基因小鼠的胸腺、皮肤或舌头中未观察到损伤的形态学证据,表明N51/KC表达诱导中性粒细胞的募集,但不诱导其炎症激活。胸腺中缺乏激活导致大量衰老的中性粒细胞群体,这些细胞被胸腺巨噬细胞和上皮网状细胞吞噬。这些结果表明N51/KC在体内是一种中性粒细胞趋化因子,并将这些转基因小鼠确立为研究中性粒细胞募集和清除现象的有效模型,这些事件对炎症反应的启动和消退至关重要。