Selectins mediate macrophage infiltration in obstructive nephropathy in newborn mice.
BACKGROUND
Urinary tract obstruction during development leads to tubular atrophy and causes interstitial fibrosis. Macrophage infiltration into the interstitium plays a central role in this process. Selectins, a family of three adhesion molecules, are involved in leukocyte recruitment to sites of inflammation and immune activity. We investigated the role of selectins in obstructive nephropathy in newborn mice.


METHODS
Triple selectin-deficient mice (EPL-/-), L-selectin deficient mice (L-/-) and wild type mice (WT) were subjected to complete unilateral ureteral obstruction (UUO) or sham operation within the first 48 hours of life, and were sacrificed 5 and 12 days later. Kidneys were removed, and sections were stained for macrophage infiltration (mAb F4/80), apoptosis (TUNEL), tubular atrophy (periodic acid-Schiff) and interstitial fibrosis (Masson trichrome).


RESULTS
Selectin deficient mice showed a marked reduction in macrophage infiltration into the obstructed kidney compared to WT at day 5 and day 12 after UUO. Tubular apoptosis was strongly reduced in EPL-/- at day 5 after UUO, and in EPL-/- and L-/- at day 12 after UUO when compared to WT. The number of apoptotic tubular cells was correlated with macrophage infiltration, suggesting that macrophages stimulate tubular apoptosis in obstructive nephropathy. In addition, tubular atrophy and interstitial fibrosis were significantly diminished in EPL-/- and L-/- compared to WT at day 12 after UUO.


CONCLUSIONS
Following UUO, selectins mediate macrophage infiltration into the obstructed kidney, which in turn may induce tubular apoptosis, tubular atrophy and interstitial fibrosis.
Lange-Sperandio
Bärbel
B
Department of Pediatrics, University of Virginia, Charlottesville, Virginia 22908-0386, USA.
Cachat
Francois
F
Thornhill
Barbara A
BA
Chevalier
Robert L
RL
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology; D001284:Atrophy; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D007674:Kidney Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D019087:Selectins / Q000235:genetics* / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D019040:E-Selectin; D019007:P-Selectin; D019087:Selectins; D019041:L-Selectin