期刊
TRANSPLANTATION
卷 83, 期 5, 页码 656-662出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.tp.0000255320.00061.e9
关键词
hematopoietic growth factor; dendritic cells; monkey; kidney; liver
资金
- NHLBI NIH HHS [HL 075512, HL 077545] Funding Source: Medline
- NIAID NIH HHS [AI 60994, AI 51698] Funding Source: Medline
- NIDDK NIH HHS [DK 49745] Funding Source: Medline
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.
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