Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS

  • Authors:
    • Benedetta Bussolati
    • Salvatore David
    • Vincenzo Cambi
    • Peter S. Tobias
    • Giovanni Camussi
  • View Affiliations

  • Published online on: October 1, 2002     https://doi.org/10.3892/ijmm.10.4.441
  • Pages: 441-449
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Abstract

Renal proximal tubular epithelial cells (PTEC) are target for LPS during sepsis and renal infections. In the present study, we evaluated whether stimulation of human PTEC by LPS is modulated through the soluble or the membrane form of the LPS receptor CD14. We found that PTEC lacked expression of the membrane form of CD14 and did not release soluble CD14 (sCD14). sCD14 was detected in the urine of normal subjects and it was increased in patients with renal sepsis or with proteinuria. In the presence of sCD14 and LPS binding protein (LBP), PTEC were 10 to 100-fold more sensitive to LPS activation, resulting in cytokine production (IL-6, IL-8 and TNF-α) and NO release. We found that sCD14 purified from urine was biologically active on PTEC. Moreover, the presence of sCD14 and LBP was required for cytotoxicity induced by low concentrations of LPS (1-10 ng/ml) in PTEC. Cell death showed the characteristics of both necrosis and apoptosis, as demonstrated by LDH release and by TUNEL and acridine orange staining and caspase-3 activation. Whereas the LPS alone was sufficient to induce necrosis, sCD14 and LBP were required for apoptosis. Our results suggest that sCD14 excreted in urine may participate with endotoxin in the activation and injury of renal proximal tubules. In particular, sCD14 may contribute to the tubulo-interstitial injury in clinical settings characterised by proteinuria and enhanced susceptibility to infections such as in diabetes.

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October 2002
Volume 10 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Bussolati B, David S, Cambi V, Tobias PS and Camussi G: Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS. Int J Mol Med 10: 441-449, 2002
APA
Bussolati, B., David, S., Cambi, V., Tobias, P.S., & Camussi, G. (2002). Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS. International Journal of Molecular Medicine, 10, 441-449. https://doi.org/10.3892/ijmm.10.4.441
MLA
Bussolati, B., David, S., Cambi, V., Tobias, P. S., Camussi, G."Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS". International Journal of Molecular Medicine 10.4 (2002): 441-449.
Chicago
Bussolati, B., David, S., Cambi, V., Tobias, P. S., Camussi, G."Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS". International Journal of Molecular Medicine 10, no. 4 (2002): 441-449. https://doi.org/10.3892/ijmm.10.4.441