Characterization of CXCL16 and ADAM10 in the normal and transplanted kidney.
The chemokine CXCL16 plays an important role in the recruitment of leukocytes to sites of inflammation influencing the course of experimental glomerulonephritis. Here we show that human kidneys highly express CXCL16 in the distal tubule, connecting tubule and principal cells of the collecting duct with weak expression in the thick ascending limb of Henle. Beside the membrane localization, a soluble form of CXCL16 can be proteolytically released which acts as a chemotactic factor. In human renal tissue the expression pattern of the disintegrin-like metalloproteinase ADAM10 is similar to that of CXCL16, suggesting ADAM10 can potentially cleave CXCL16 in vivo. When we tested this in primary tubular cells we found that blockade of ADAM10 activity inhibited the IFN-gamma induced release of soluble CXCL16. Acute tubular damage in renal allografts was associated with elevated urinary CXCL16 and this correlated with focally increased apical CXCL16 expression in the distal tubules and collecting ducts. Renal allograft biopsies, with a histopathological diagnosis of acute interstitial rejection, showed increased basolateral ADAM10 expression together with high numbers of infiltrating T cells. Our results suggest that CXCL16 and ADAM10 are involved in the recruitment of T cells to the kidney and play an important role in inflammatory kidney diseases.
Schramme
Anja
A
1pharmazentrum frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Abdel-Bakky
Mohamed Sadek
MS
Gutwein
Paul
P
Obermüller
Nicholas
N
Baer
Patrick C
PC
Hauser
Ingeborg A
IA
Ludwig
Andreas
A
Gauer
Stefan
S
Schäfer
Liliana
L
Sobkowiak
Ewelina
E
Altevogt
Peter
P
Koziolek
Michael
M
Kiss
Eva
E
Gröne
Hermann-Josef
HJ
Tikkanen
Ritva
R
Goren
Itamar
I
Radeke
Heinfried
H
Pfeilschifter
Josef
J
D051722:ADAM Proteins / Q000276:immunology / Q000378:metabolism*; D000072197:ADAM10 Protein; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000276:immunology / Q000378:metabolism*; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism* / Q000652:urine; D002634:Chemotaxis, Leukocyte; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D051116:Receptors, Scavenger / Q000276:immunology / Q000378:metabolism*; D012995:Solubility; D013601:T-Lymphocytes / Q000502:physiology
C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; D051116:Receptors, Scavenger; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human