PMID- 22882940 OWN - NLM STAT- MEDLINE DCOM- 20130102 LR - 20161125 IS - 2542-5641 (Electronic) IS - 0366-6999 (Linking) VI - 125 IP - 14 DP - 2012 Jul TI - In vivo administration of Fms-like tyrosine kinase-3 ligand effectively stimulates lung dendritic cell expansion in mice. PG - 2562-7 AB - BACKGROUND: Dendritic cells (DCs) are the most important professional antigen presenting cells that play a key role in initiating adaptive immune responses. The depletion and dysfunction of DCs contribute to the development of immunodeficiency or immunoparalysis in some lung diseases. In the present study, we investigated the effects of Fms-like tyrosine kinase-3 ligand (Flt3L) administration in vivo on lung DCs expansion to provide an experimental basis of Flt3L used as a potential therapeutic agent for the related lung disorders. METHODS: Balb/c mice were randomly divided into Flt3L group (n = 10) and control group (n = 10). Each mouse in the Flt3L group received subcutaneous administration of Flt3L at a dose of 10 microg once daily for nine consecutive days. Lung histology was observed, and CD11c and CD205 were immunologically labeled in lung tissue sections. Low-density lung cells were separated by density gradient centrifugation, and then subsets and MHC-II/I-A(d) expression of DCs were analyzed by flow cytometry. RESULTS: In the Flt3L group the number and density of DC-like cells were markedly increased compared with the control group, mainly distributed in the alveolar septa. Immunological labeling in situ found that there were significantly higher numbers of CD11c(+) and CD205(+) DCs in lung mesenchymal tissue (P < 0.05), where they formed a denser reticular formation. Flow cytometry analysis demonstrated that the proportions of myeloid CD11c(+)CD11b(+) DCs and plasmacytoid CD11c(+)CD45R/B220(+) DCs in the low-density lung cells in the Flt3L group were significantly higher compared with the control group; showing 3.17- and 3.3-fold increase respectively (P < 0.05). The proportion of CD11c(+) DCs expressing MHC-II/I-A(d+) was significantly increased, with a 2.7-fold increase as compared with the control group (P < 0.05). CONCLUSIONS: Flt3L administration in vivo induces lung DCs expansion, favoring myeloid and plasmacytoid DC subsets, which are phenotypically more mature. Flt3L may be useful in the therapy to augment immune function of the lung. FAU - Wang, Hong-Wei AU - Wang HW AD - Department of Pathology, First Affiliated Hospital of General Hospital of People's Liberation Army, Beijing 100048, China. FAU - Lu, Jiang-Yang AU - Lu JY FAU - Wang, Lin AU - Wang L FAU - Tian, Guang AU - Tian G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Chin Med J (Engl) JT - Chinese medical journal JID - 7513795 RN - 0 (Antigens, CD) RN - 0 (DEC-205 receptor) RN - 0 (Lectins, C-Type) RN - 0 (Membrane Proteins) RN - 0 (Minor Histocompatibility Antigens) RN - 0 (Receptors, Cell Surface) RN - 0 (flt3 ligand protein) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Cells, Cultured MH - Dendritic Cells/*drug effects/metabolism/ultrastructure MH - Flow Cytometry MH - Immunohistochemistry MH - Lectins, C-Type/metabolism MH - Lung/*drug effects/metabolism/ultrastructure MH - Male MH - Membrane Proteins/*pharmacology MH - Mice MH - Mice, Inbred BALB C MH - Microscopy, Electron, Transmission MH - Minor Histocompatibility Antigens MH - Random Allocation MH - Receptors, Cell Surface/metabolism EDAT- 2012/08/14 06:00 MHDA- 2013/01/03 06:00 CRDT- 2012/08/14 06:00 PHST- 2012/08/14 06:00 [entrez] PHST- 2012/08/14 06:00 [pubmed] PHST- 2013/01/03 06:00 [medline] PST - ppublish SO - Chin Med J (Engl). 2012 Jul;125(14):2562-7.