Neutrophil fate in experimental glomerular capillary injury in the rat. Emigration exceeds in situ clearance by apoptosis.
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.
Hughes
J
J
Department of Medicine, University Hospital, Nottingham, United Kingdom.
Johnson
R J
RJ
Mooney
A
A
Hugo
C
C
Gordon
K
K
Savill
J
J
D000818:Animals; D017209:Apoptosis; D002196:Capillaries / Q000473:pathology; D002465:Cell Movement; D003208:Concanavalin A / Q000633:toxicity; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007205:Indium Radioisotopes; D007262:Infusions, Intravenous; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D007205:Indium Radioisotopes; D003208:Concanavalin A