Hughes J, Johnson R J, Mooney A, Hugo C, Gordon K, Savill J
Department of Medicine, University Hospital, Nottingham, United Kingdom.
Am J Pathol. 1997 Jan;150(1):223-34.
Neutrophils (PMNs) and their toxic contents can injure glomeruli, but to date their fate in glomerulonephritis has been unknown. We studied glomerulonephritis induced in rats by formation of concanavalin A (Con A)/anti-Con A immune complexes on glomerular endothelial cells. PMN infiltration, which was almost exclusively confined to the lumen of glomerular capillaries, was transient, peaking at 4 hours, with only 9.0 +/- 4.1% (mean +/- SEM) of the maximum remaining at 24 hours. There was clear evidence of PMN apoptosis leading to phagocytosis in situ by intraluminal macrophages. However, the kinetics of leukocyte infiltration and PMN apoptosis, the preferential location at 24 hours of apoptotic PMNs within occluded capillary loops, and tracking of radiolabeled PMNs all indicated that in situ phagocytic clearance after apoptosis was the fate of a minority of PMNs, amounting to no more than one-fifth of the peak infiltrating load. Instead, the majority of infiltrating PMNs (72.9 +/- 3.1%) had emigrated from inflamed glomeruli by 24 hours, apparently returning to the circulation. We conclude that PMN emigration from inflamed glomeruli is a hitherto unrecognized mechanism for regulation of PMN-mediated glomerular injury.
中性粒细胞（PMN）及其毒性成分可损伤肾小球，但迄今为止它们在肾小球肾炎中的命运尚不清楚。我们研究了通过在肾小球内皮细胞上形成伴刀豆球蛋白A（Con A）/抗Con A免疫复合物诱导大鼠发生的肾小球肾炎。PMN浸润几乎完全局限于肾小球毛细血管腔内，是短暂的，在4小时达到峰值，24小时时仅剩余最大值的9.0±4.1%（平均值±标准误）。有明确证据表明PMN发生凋亡并导致腔内巨噬细胞原位吞噬。然而，白细胞浸润和PMN凋亡的动力学、凋亡PMN在24小时时在闭塞毛细血管袢内的优先定位以及放射性标记PMN的追踪均表明，凋亡后的原位吞噬清除是少数PMN的命运，不超过峰值浸润负荷的五分之一。相反，到24小时时，大多数浸润的PMN（72.9±3.1%）已从炎症肾小球中移出，显然返回了循环系统。我们得出结论，PMN从炎症肾小球中移出是一种迄今为止未被认识的调节PMN介导的肾小球损伤的机制。
