Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction.
Mononuclear cells infiltrating the interstitium are involved in renal tubulointerstitial injury. The unilateral ureteral obstruction (UUO) is an established experimental model of renal interstitial inflammation. In our previous study, we postulated that L-selectin on monocytes is involved in their infiltration into the interstitium by UUO and that a sulfated glycolipid, sulfatide, is the physiological L-selectin ligand in the kidney. Here we tested the above hypothesis using sulfatide- and L-selectin-deficient mice. Sulfatide-deficient mice were generated by gene targeting of the cerebroside sulfotransferase (Cst) gene. Although the L-selectin-IgG chimera protein specifically bound to sulfatide fraction in acidic lipids from wild-type kidney, it did not show such binding in fractions of Cst(-/-) mice kidney, indicating that sulfatide is the major L-selectin-binding glycolipid in the kidney. The distribution of L-selectin ligand in wild-type mice changed after UUO; sulfatide was relocated from the distal tubules to the peritubular capillaries where monocytes infiltrate, suggesting that sulfatide relocated to the endothelium after UUO interacted with L-selectin on monocytes. In contrast, L-selectin ligand was not detected in Cst(-/-) mice irrespective of UUO treatment. Compared with wild-type mice, Cst(-/-) mice showed a considerable reduction in the number of monocytes/macrophages that infiltrated the interstitium after UUO. The number of monocytes/macrophages was also reduced to a similar extent in L-selectin(-/-) mice. Our results suggest that sulfatide is a major L-selectin-binding molecule in the kidney and that the interaction between L-selectin and sulfatide plays a critical role in monocyte infiltration into the kidney interstitium.
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Daisuke
D
Ogawa
Kenichi
K
Shikata
Koichi
K
Honke
Shinichi
S
Sato
Mitsuhiro
M
Matsuda
Ryo
R
Nagase
Atsuhito
A
Tone
Shinichi
S
Okada
Hitomi
H
Usui
Jun
J
Wada
Masayuki
M
Miyasaka
Hiroto
H
Kawashima
Yasuo
Y
Suzuki
Takashi
T
Suzuki
Naoyuki
N
Taniguchi
Yukie
Y
Hirahara
Keiko
K
Tadano-Aritomi
Ineo
I
Ishizuka
Thomas F
TF
Tedder
Hirofumi
H
Makino
D000818:Animals; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D019041:L-Selectin / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D013433:Sulfoglycosphingolipids / Q000378:metabolism; D015238:Sulfotransferases / Q000172:deficiency / Q000502:physiology*; D014517:Ureteral Obstruction / Q000473:pathology*
D007074:Immunoglobulin G; D013433:Sulfoglycosphingolipids; D019041:L-Selectin; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase