PMID- 18694997
OWN - NLM
STAT- MEDLINE
DCOM- 20081112
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 112
IP  - 9
DP  - 2008 Nov 1
TI  - Divergent effects of hypoxia on dendritic cell functions.
PG  - 3723-34
LID - 10.1182/blood-2008-02-142091 [doi]
AB  - Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that 
      patrol tissues to sense danger signals and activate specific immune responses. In 
      addition, they also play a role in inflammation and tissue repair. Here, we show 
      that oxygen availability is necessary to promote full monocyte-derived DC 
      differentiation and maturation. Low oxygen tension (hypoxia) inhibits expression 
      of several differentiation and maturation markers (CD1a, CD40, CD80, CD83, CD86, 
      and MHC class II molecules) in response to lipopolysaccharide (LPS), as well as 
      their stimulatory capacity for T-cell functions. These events are paralleled by 
      impaired up-regulation of the chemokine receptor CCR7, an otherwise necessary 
      event for the homing of mature DCs to lymph nodes. In contrast, hypoxia strongly 
      up-regulates production of proinflammatory cytokines, particularly TNFalpha and 
      IL-1beta, as well as the inflammatory chemokine receptor CCR5. Subcutaneous 
      injection of hypoxic DCs into the footpads of mice results in defective DC homing 
      to draining lymph nodes, but enhanced leukocyte recruitment at the site of 
      injection. Thus, hypoxia uncouples the promotion of inflammatory and tissue 
      repair from sentinel functions in DCs, which we suggest is a safeguard mechanism 
      against immune reactivity to damaged tissues.
FAU - Mancino, Alessandra
AU  - Mancino A
AD  - Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico 
      (IRCCS), Milan, Italy.
FAU - Schioppa, Tiziana
AU  - Schioppa T
FAU - Larghi, Paola
AU  - Larghi P
FAU - Pasqualini, Fabio
AU  - Pasqualini F
FAU - Nebuloni, Manuela
AU  - Nebuloni M
FAU - Chen, I-Hsuan
AU  - Chen IH
FAU - Sozzani, Silvano
AU  - Sozzani S
FAU - Austyn, Jonathan M
AU  - Austyn JM
FAU - Mantovani, Alberto
AU  - Mantovani A
FAU - Sica, Antonio
AU  - Sica A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080811
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Hypoxia/*immunology/*physiology
MH  - Cells, Cultured
MH  - Chemokines/metabolism
MH  - Chemotaxis
MH  - Cytokines/metabolism
MH  - Dendritic Cells/cytology/drug effects/*immunology/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Inflammation/immunology/metabolism/pathology
MH  - Ligands
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocytes/cytology/immunology/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Toll-Like Receptors/agonists/genetics/metabolism
EDAT- 2008/08/13 09:00
MHDA- 2008/11/13 09:00
CRDT- 2008/08/13 09:00
PHST- 2008/08/13 09:00 [pubmed]
PHST- 2008/11/13 09:00 [medline]
PHST- 2008/08/13 09:00 [entrez]
AID - S0006-4971(20)51932-0 [pii]
AID - 10.1182/blood-2008-02-142091 [doi]
PST - ppublish
SO  - Blood. 2008 Nov 1;112(9):3723-34. doi: 10.1182/blood-2008-02-142091. Epub 2008 
      Aug 11.