PMID- 18364398
OWN - NLM
STAT- MEDLINE
DCOM- 20080903
LR  - 20171116
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 22
IP  - 8
DP  - 2008 Aug
TI  - Lactoferrin, a major defense protein of innate immunity, is a novel maturation 
      factor for human dendritic cells.
PG  - 2747-57
LID - 10.1096/fj.07-098038 [doi]
AB  - Lactoferrin (LF) is an important protein component of the innate immune system 
      that is broadly distributed within the body fluids. LF is endowed with multiple 
      biological activities. Talactoferrin (TLF), a recombinant human LF, is in 
      clinical development as an anticancer agent and is entering Phase III clinical 
      trials. Here, we show that TLF induces the maturation of human dendritic cells 
      (DCs) derived from monocytes. TLF, at physiologically relevant concentrations 
      (100 microg/ml) up-regulates the expression of human leukocyte antigen (HLA) 
      class II, CD83, CD80, and CD86 costimulatory molecule and CXCR4 and CCR7 
      chemokine receptors, acting primarily through the p38 MAPK signaling pathway. DCs 
      matured by TLF displayed an enhanced release of IL-8 and CXCL10, as well as a 
      significantly reduced production of IL-6, IL-10, and CCL20. They also display a 
      reduced ability to take up antigen and increased capacity to trigger 
      proliferation and release IFN-gamma in the presence of allogeneic human T cells. 
      TLF-matured DCs are able to prime naive T cells to respond to KLH antigen and 
      display a significantly increased capacity to present Flu-MA(58-66) peptide to 
      HLA-A2-matched T cells. These data suggest that a key immunomodulatory function 
      that may be mediated by TLF is to link the innate with adaptive immunity through 
      DC maturation.
FAU - Spadaro, Michela
AU  - Spadaro M
AD  - Molecular Biotechnology Center, Department of Clinical and Biological Science, 
      University of Turin, 10126 Torino, Italy.
FAU - Caorsi, Cristiana
AU  - Caorsi C
FAU - Ceruti, Patrizia
AU  - Ceruti P
FAU - Varadhachary, Atul
AU  - Varadhachary A
FAU - Forni, Guido
AU  - Forni G
FAU - Pericle, Federica
AU  - Pericle F
FAU - Giovarelli, Mirella
AU  - Giovarelli M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080325
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Cytokines)
RN  - 0 (Recombinant Proteins)
RN  - 7A055A9QRR (talactoferrin alfa)
RN  - EC 3.4.21.- (Lactoferrin)
SB  - IM
MH  - Cell Differentiation/drug effects
MH  - Cytokines/metabolism
MH  - Dendritic Cells/cytology/*drug effects/immunology
MH  - Humans
MH  - Immunity, Innate
MH  - In Vitro Techniques
MH  - Lactoferrin/immunology/*pharmacology
MH  - Lymphocyte Activation/drug effects
MH  - Models, Biological
MH  - Monocytes/cytology/drug effects/immunology
MH  - Recombinant Proteins/immunology/pharmacology
MH  - T-Lymphocytes/drug effects/immunology
EDAT- 2008/03/28 09:00
MHDA- 2008/09/04 09:00
CRDT- 2008/03/28 09:00
PHST- 2008/03/28 09:00 [pubmed]
PHST- 2008/09/04 09:00 [medline]
PHST- 2008/03/28 09:00 [entrez]
AID - fj.07-098038 [pii]
AID - 10.1096/fj.07-098038 [doi]
PST - ppublish
SO  - FASEB J. 2008 Aug;22(8):2747-57. doi: 10.1096/fj.07-098038. Epub 2008 Mar 25.