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 M(w) of 15kDa [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 M(w) 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.
Richter
Rudolf
R
IPF PharmaCeuticals GmbH, Hannover, Germany. Rudorichter@gmx.de
Forssmann
Ulf
U
Henschler
Reinhard
R
Escher
Sylvia
S
Frimpong-Boateng
Adjoa
A
Forssmann
Wolf-Georg
WG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D019742:Chemokines, CC / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006440:Hemofiltration; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D019402:Macrophage Inflammatory Proteins; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015846:Monokines / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D006435:Renal Dialysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C108814:CCL15 protein, human; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D010446:Peptide Fragments; D002118:Calcium