Deficiency of P-selectin or P-selectin glycoprotein ligand-1 leads to accelerated development of glomerulonephritis and increased expression of CC Chemokine Ligand 2 in lupus-prone mice

Xiaodong He, Trenton R Schoeb, Angela Panoskaltsis-Mortari, Kurt R Zinn, Robert A Kesterson, Junxuan Zhang, Sharon Samuel, M John Hicks, Michael John Hickey, Daniel C Bullard

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Abstract

The selectins and their ligands mediate leukocyte rolling on endothelial cells, the initial step in the emigration cascade leading to leukocyte infiltration of tissue. These adhesion molecules have been shown to be key promoters of acute leukocyte emigration events; however, their roles in the development of long-term inflammatory responses, including those that occur during chronic inflammatory diseases such as systemic lupus erythematosus, are unclear. To assess participation of P-selectin in such disorders, we studied the progression of systemic lupus erythematosus-like disease in P-selectin-deficient and control MRL/MpJ-Fas(lpr) (Fas(lpr)) mice. Surprisingly, we found that P-selectin deficiency resulted in significantly earlier mortality, characterized by a more rapid development of glomerulonephritis and dermatitis. Expression of CCL2 (MCP-1) was increased in the kidneys of P-selectin mutant mice and in supernatants of LPS-stimulated primary renal endothelial cell cultures from these mice. A closely similar phenotype, including elevated renal expression of CCL2, was also observed in Fas(lpr) mice deficient in the major P-selectin ligand, P-selectin glycoprotein ligand-1. These results indicate that P-selectin and P-selectin glycoprotein ligand-1 are not required for leukocyte infiltration and the development of autoimmune disease in Fas(lpr) mice, but rather expression of these adhesion molecules is important for modulating the progression of glomerulonephritis, possibly through down-regulation of endothelial CCL2 expression.
Original languageEnglish
Pages (from-to)8748 - 8756
Number of pages9
JournalJournal of Immunology
Volume177
Issue number12
Publication statusPublished - 2006

Cite this

He, X., Schoeb, T. R., Panoskaltsis-Mortari, A., Zinn, K. R., Kesterson, R. A., Zhang, J., Samuel, S., Hicks, M. J., Hickey, M. J., & Bullard, D. C. (2006). Deficiency of P-selectin or P-selectin glycoprotein ligand-1 leads to accelerated development of glomerulonephritis and increased expression of CC Chemokine Ligand 2 in lupus-prone mice. Journal of Immunology, 177(12), 8748 - 8756.