MIP-3alpha/CCL20 in renal transplantation and its possible involvement as dendritic cell chemoattractant in allograft rejection.
Graft-infiltrating dendritic cells (DC) and alloreactive T lymphocytes play a critical role in renal allograft rejection. Renal proximal tubular epithelial cells (TEC) are considered as active players in the attraction of leukocytes during renal inflammatory responses. Macrophage inflammatory protein (MIP)-3alpha/CCL20 is a major chemokine expressed by epithelial cells that attracts immature DC. In the present study, we present evidence that also the transplanted kidney can be a major source of MIP-3alpha/CCL20. Renal transplant recipients with rejection showed significantly increased excretion of urinary MIP-3alpha/CCL20 that correlated with transplant function. The tubular staining for MIP-3alpha/CCL20 in renal biopsies of patients with rejection as well as in vitro studies with primary human TEC indicated that TEC might be responsible for the increased urinary MIP-3alpha/CCL20. Furthermore, MIP-3alpha/CCL20 produced by activated TEC was highly potent in the attraction of CD1a+CD34+-derived DC precursors. These data suggest a role for MIP-3alpha/CCL20 in amplification of the immune response during renal allograft rejection by attraction of CCR6+ inflammatory cells, which may include DC, to the site of inflammation.
Woltman
Andrea M
AM
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. A.M.Woltman@lumc.nl
de Fijter
Johan W
JW
van der Kooij
Sandra W
SW
Jie
Kim E
KE
Massacrier
Catherine
C
Caux
Christophe
C
Daha
Mohamed R
MR
van Kooten
Cees
C
D000328:Adult; D018949:Antigens, CD1 / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D001706:Biopsy; D023201:CD40 Ligand / Q000096:biosynthesis; D002465:Cell Movement; D054418:Chemokine CCL20; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis*; D002630:Chemotactic Factors; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006084:Graft Rejection; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D007684:Kidney Tubules / Q000473:pathology; D007962:Leukocytes / Q000166:cytology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods*
D018949:Antigens, CD1; D018952:Antigens, CD34; C108355:CCL20 protein, human; C483024:CCL5 protein, human; C498126:CCR6 protein, mouse; C419393:CD1a antigen; D054418:Chemokine CCL20; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D002630:Chemotactic Factors; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D023201:CD40 Ligand