Cerebroside Sulfotransferase Deficiency Ameliorates L-selectin-dependent Monocyte Infiltration in the Kidney after Ureteral Obstruction

Daisuke Ogawa, Kenichi Shikata, Koichi Honke, Shinichi Sato, Mitsuhiro Matsuda, Ryo Nagase, Atsuhito Tone, Shinichi Okada, Hitomi Usui, Jun Wada, Masayuki Miyasaka, Hiroto Kawashima, Yasuo Suzuki, Takashi Suzuki, Naoyuki Taniguchi, Yukie Hirahara, Keiko Tadano-Aritomi, Ineo Ishizuka, Thomas F. Tedder, Hirofumi Makino

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Abstract

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.

Original languageEnglish
Pages (from-to)2085-2090
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number3
DOIs
Publication statusPublished - Jan 16 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ogawa, D., Shikata, K., Honke, K., Sato, S., Matsuda, M., Nagase, R., Tone, A., Okada, S., Usui, H., Wada, J., Miyasaka, M., Kawashima, H., Suzuki, Y., Suzuki, T., Taniguchi, N., Hirahara, Y., Tadano-Aritomi, K., Ishizuka, I., Tedder, T. F., & Makino, H. (2004). Cerebroside Sulfotransferase Deficiency Ameliorates L-selectin-dependent Monocyte Infiltration in the Kidney after Ureteral Obstruction. Journal of Biological Chemistry, 279(3), 2085-2090. https://doi.org/10.1074/jbc.M305809200