Haraoka M, Hang L, Frendéus B, Godaly G, Burdick M, Strieter R, Svanborg C
Institute of Laboratory Medicine, Section of Microbiology, Lund University, Sweden.
J Infect Dis. 1999 Oct;180(4):1220-9. doi: 10.1086/315006.
This study examined the role of neutrophil leukocytes for the antibacterial defense at mucosal infection sites. Urinary tract infection (UTI) was established by injection into the bladder lumen of Escherichia coli 1177, a fully virulent clinical isolate. Infection of C3H/HeN (lpsn, lpsn) mice recruited neutrophils into the urinary tract, and bacteria were cleared from kidneys and bladders. The neutrophil response was absent in C3H/HeJ (lpsd, lpsd) mice, and bacteria persisted in the tissues. Peripheral neutrophil depletion of C3H/HeN mice was subsequently achieved by pretreatment with the granulocyte-specific antibody RB6-8C5. The E. coli-induced neutrophil recruitment was inhibited, as shown by immunohistochemistry and tissue myeloperoxidase quantitation. As a consequence, bacterial clearance from kidneys and bladders was drastically impaired. Antibody treatment of C3H/HeJ mice had only a marginal effect. The results show that neutrophils are essential for bacterial clearance from the urinary tract and that the neutrophil recruitment deficiency in C3H/HeJ mice explains their susceptibility to gram-negative UTI.
本研究考察了中性粒细胞在黏膜感染部位抗菌防御中的作用。通过向膀胱腔内注射完全有毒力的临床分离株大肠杆菌1177建立尿路感染(UTI)模型。C3H/HeN(lpsn,lpsn)小鼠感染后,中性粒细胞被募集到尿路中,细菌从肾脏和膀胱中清除。C3H/HeJ(lpsd,lpsd)小鼠没有中性粒细胞反应,细菌在组织中持续存在。随后,通过用粒细胞特异性抗体RB6-8C5预处理实现C3H/HeN小鼠外周血中性粒细胞耗竭。免疫组织化学和组织髓过氧化物酶定量分析表明,大肠杆菌诱导的中性粒细胞募集受到抑制。结果,肾脏和膀胱的细菌清除受到严重损害。抗体处理对C3H/HeJ小鼠只有轻微影响。结果表明,中性粒细胞对于从尿路清除细菌至关重要,C3H/HeJ小鼠中性粒细胞募集缺陷解释了它们对革兰氏阴性菌UTI的易感性。