MESANGIAL CELL APOPTOSIS - THE MAJOR MECHANISM FOR RESOLUTION OF GLOMERULAR HYPERCELLULARITY IN EXPERIMENTAL MESANGIAL PROLIFERATIVE NEPHRITIS

被引:403
作者
BAKER, AJ
MOONEY, A
HUGHES, J
LOMBARDI, D
JOHNSON, RJ
SAVILL, J
机构
[1] UNIV NOTTINGHAM HOSP, DEPT MED, DIV RENAL & INFLAMMATORY DIS, NOTTINGHAM NG7 2UH, ENGLAND
[2] HAMMERSMITH HOSP, ROYAL POSTGRAD MED SCH, DEPT MED, RENAL UNIT, LONDON W12 0NN, ENGLAND
[3] UNIV WASHINGTON, DEPT MED, DIV NEPHROL, SEATTLE, WA 98195 USA
基金
英国惠康基金;
关键词
MESANGIAL CELL; APOPTOSIS; GLOMERULONEPHRITIS; RESOLUTION; INJURY;
D O I
10.1172/JCI117565
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Increases in mesangial cell number may herald glomerular scarring, but they are not irreversible. This study sought mechanisms by which surplus glomerular mesangial cells can be cleared. A small proportion of cultured mesangial cells exhibited typical morphological features of apoptosis (programmed cell death), which was increased by growth factor deprivation or exposure to cycloheximide, stimuli known to increase apoptosis in other cell types. Apoptosis was confirmed by typical internucleosomal chromatin cleavage. In vivo, clear morphological evidence of mesangial apoptosis leading to phagocytosis by neighboring mesangial cells was obtained in self-limited mesangial proliferation induced in rats by Thy1.1 antibody, apoptosis occurring similar to 10-fold more frequently than in the healthy rat glomerulus. Indeed, changes in glomerular cell number in Thy1.1 nephritis strongly suggested that apoptosis is the major cell clearance mechanism counterbalancing cell division, thereby mediating resolution of glomerular hypercellularity in experimental mesangial proliferation.
引用
收藏
页码:2105 / 2116
页数:12
相关论文
共 53 条
[41]   SOCIAL CONTROLS ON CELL-SURVIVAL AND CELL-DEATH [J].
RAFF, MC .
NATURE, 1992, 356 (6368) :397-400
[42]   THROMBOSPONDIN COOPERATES WITH CD36 AND THE VITRONECTIN RECEPTOR IN MACROPHAGE RECOGNITION OF NEUTROPHILS UNDERGOING APOPTOSIS [J].
SAVILL, J ;
HOGG, N ;
REN, Y ;
HASLETT, C .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (04) :1513-1522
[43]   GLOMERULAR MESANGIAL CELLS AND INFLAMMATORY MACROPHAGES INGEST NEUTROPHILS UNDERGOING APOPTOSIS [J].
SAVILL, J ;
SMITH, J ;
SARRAF, C ;
REN, Y ;
ABBOTT, F ;
REES, A .
KIDNEY INTERNATIONAL, 1992, 42 (04) :924-936
[44]   VITRONECTIN RECEPTOR-MEDIATED PHAGOCYTOSIS OF CELLS UNDERGOING APOPTOSIS [J].
SAVILL, J ;
DRANSFIELD, I ;
HOGG, N ;
HASLETT, C .
NATURE, 1990, 343 (6254) :170-173
[45]   MACROPHAGE PHAGOCYTOSIS OF AGING NEUTROPHILS IN INFLAMMATION - PROGRAMMED CELL-DEATH IN THE NEUTROPHIL LEADS TO ITS RECOGNITION BY MACROPHAGES [J].
SAVILL, JS ;
WYLLIE, AH ;
HENSON, JE ;
WALPORT, MJ ;
HENSON, PM ;
HASLETT, C .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (03) :865-875
[46]  
SCHUMER M, 1992, AM J PATHOL, V140, P831
[47]   CILIARY NEUROTROPHIC FACTOR PREVENTS THE DEGENERATION OF MOTOR NEURONS AFTER AXOTOMY [J].
SENDTNER, M ;
KREUTZBERG, GW ;
THOENEN, H .
NATURE, 1990, 345 (6274) :440-441
[48]   MESANGIAL CELLS EXPRESS PDGF MESSENGER-RNAS AND PROLIFERATE IN RESPONSE TO PDGF [J].
SHULTZ, PJ ;
DICORLETO, PE ;
SILVER, BJ ;
ABBOUD, HE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (04) :F674-F684
[49]  
STRIKER LJ, 1991, LAB INVEST, V64, P446
[50]   TRANSIENT ELEVATIONS OF CYTOSOLIC-FREE CALCIUM RETARD SUBSEQUENT APOPTOSIS IN NEUTROPHILS IN-VITRO [J].
WHYTE, MKB ;
HARDWICK, SJ ;
MEAGHER, LC ;
SAVILL, JS ;
HASLETT, C .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (01) :446-455