Growth factor-induced mobilization of dendritic cells in kidney and liver of rhesus macaques: implications for transplantation.
Hematopoietic growth factors (HGF) mobilize potential tolerogenic cells in transplant donors. Fms-like tyrosine kinase 3 ligand (Flt3L) mobilizes stem cells and dendritic cells (DCs) in human and nonhuman primate blood. Blood and renal and liver biopsies were obtained from untreated and Flt3L-mobilized rhesus macaques. Flt3L increased the number of myeloid CD11c(hi) and plasmacytoid CD123(hi) precursors in blood and both myeloid CD11c(+) HLA-DR(+) fascin(+) (CD45RA(-)) DCs and putative plasmacytoid CD11c(lo) CD45RA(hi) DC precursors in liver and kidneys, without affecting organ function. DC in Flt3L-treated monkeys were concentrated in the glomeruli and interstitium of kidneys, and in the portal triads and parenchyma of liver. These DCs exhibited the phenotype of immature antigen-presenting cells (APCs; CD83(-) CD86(lo) CCR5(+) CCR7(-)). HGF-induced changes reversed significantly within 7 days of Flt3L withdrawal. Therapeutic protocols that mobilize donor hematopoietic cells should consider the influence of HGF on the APC constituency of prospective organ allografts.
Morelli
Adrian E
AE
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Coates
P Toby H
PT
Shufesky
William J
WJ
Barratt-Boyes
Simon M
SM
Fung
John J
JJ
Demetris
Anthony J
AJ
Thomson
Angus W
AW
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D001691:Biological Therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006133:Growth Substances / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000627:therapeutic use; D023421:Models, Animal
D000276:Adjuvants, Immunologic; D006133:Growth Substances; D008565:Membrane Proteins; C084881:flt3 ligand protein