Increase of expression and activation of chemokine CCL15 in chronic renal failure

Chemokines are believed to be involved in the pathogenesis of chronic renal failure (CRF). In CRF, significantly increased CCL15-IR plasma concentrations were detected. Whereas in plasma of healthy individuals one predominant CCL15-IR molecule with a Mw of 15 kDa [high molecular weight (HMW-CCL15-IR)] was identified, CRF plasma contains increased concentrations of truncated CCL15-IR molecules [intermediate molecular weight (IMW-CCL15-IR)]. HMW-CCL15-IR isolated from hemofiltrate revealed an Mw of 10141.3, corresponding to deglycosylated CCL15(1-92) carrying a N-terminal pyrrolidone carboxylic acid. CCL15(12-92) was identified as a major component of IMW-CCL15-IR in CRF plasma. Compared to CCL15(1-92), in monocytes CCL15(12-92) causes stronger induction of intracellular calcium flux, chemotactic activity, and adhesion to fibronectin. Intracellular calcium flux assays revealed that, in comparison to peripheral blood mononuclear cells (PBMC) of healthy donors, PBMCs of CRF patients demonstrated an increased sensitivity to CCL15. Our results point to an involvement of the CCL15–CCR1 axis in the pathophysiology of CRF.