Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury.
Renal ischemia-reperfusion injury (IRI) rapidly induces production of inflammatory mediators including, and in particular, tumor necrosis factor (TNF). Possible sources include resident parenchymal and bone marrow-derived cells as well as recruited leukocytes. Cell suspensions from kidneys subjected to IRI were examined by cell separation followed by in vitro culture and enzyme-linked immunosorbent assay (ELISA), immunoperoxidase and immunofluorescence microscopy, and multicolor flow cytometry to determine the contribution of dendritic cells (DCs) to early production of TNF and other inflammatory mediators. Secretion of TNF, interleukin (IL-6), monocyte chemoattractant protein-1 (MCP-1), and regulated on activation normal T cell expressed and secreted (RANTES) was increased in cell suspensions from IRI compared with control kidneys and was higher in DC-enriched preparations. Immunostaining identified TNF(+ve) cells that coexpressed the DC marker CD11c. Flow cytometry of bone marrow-derived (CD45(+ve)) cell populations at 24 h post-IRI demonstrated that F4/80(+ve)/CD11c(+ve) DCs remained proportionately stable and exhibit higher levels of DC maturation markers, whereas the proportion of F4/80(-ve) DCs, monocytes, neutrophils, and T cells increased. Intracellular staining for TNF confirmed that F4/80(+ve) DCs were the predominant TNF(+ve) cell and expressed higher levels than other TNF(+ve) cells. In vivo depletion of DCs from the kidney substantially attenuated TNF secretion by total and CD45(+ve) cells following IRI. The results uncover a role for resident F4/80(+ve) DCs as the predominant secretors of TNF within 24 h of IRI.
Dong
X
X
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Swaminathan
S
S
Bachman
L A
LA
Croatt
A J
AJ
Nath
K A
KA
Griffin
M D
MD
D000818:Animals; D018845:CD11 Antigens / Q000096:biosynthesis; D003713:Dendritic Cells / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018845:CD11 Antigens; D014409:Tumor Necrosis Factor-alpha