Hang L, Frendéus B, Godaly G, Svanborg C
Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
J Infect Dis. 2000 Dec;182(6):1738-48. doi: 10.1086/317599. Epub 2000 Nov 8.
Interleukin (IL)-8 receptor knockout (KO) mice were shown to have a dysfunctional neutrophil response to urinary tract infection and to develop renal scarring. Intravesical Escherichia coli infection stimulated epithelial chemokine secretion and IL-8 receptor expression in control mice. Neutrophils migrated through the tissues and crossed the epithelial barrier into the urinary tract lumen. In murine IL-8 receptor homologue (mIL-8Rh) KO mice, infection triggered a chemokine response, and neutrophils were recruited but failed to traverse the mucosal barrier and accumulated under the epithelium. After 7 days, control mice were healthy, and infection was cleared, but mIL-8Rh KO mice had swollen kidneys, with neutrophil abscesses and high numbers of bacteria. After 35 days, they developed kidney pathology and renal scarring. The results demonstrate that chemokine receptors drive transepithelial neutrophil migration. In their absence, the neutrophils are trapped, and the tissues are destroyed. This molecular deficiency may determine the progression from acute pyelonephritis to renal scarring.
白细胞介素（IL）-8受体基因敲除（KO）小鼠对尿路感染的中性粒细胞反应功能失调，并会出现肾瘢痕形成。膀胱内大肠杆菌感染刺激对照小鼠上皮细胞分泌趋化因子并表达IL-8受体。中性粒细胞穿过组织并跨越上皮屏障进入尿路管腔。在小鼠IL-8受体同源物（mIL-8Rh）基因敲除小鼠中，感染引发趋化因子反应，中性粒细胞被募集，但未能穿过黏膜屏障并在上皮下积聚。7天后，对照小鼠健康，感染清除，但mIL-8Rh基因敲除小鼠的肾脏肿大，有中性粒细胞脓肿和大量细菌。35天后，它们出现肾脏病变和肾瘢痕形成。结果表明趋化因子受体驱动跨上皮中性粒细胞迁移。在缺乏趋化因子受体的情况下，中性粒细胞被困住，组织被破坏。这种分子缺陷可能决定了从急性肾盂肾炎到肾瘢痕形成的病程进展。
