PMID- 23192608
OWN - NLM
STAT- MEDLINE
DCOM- 20130827
LR  - 20211021
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 114
IP  - 5
DP  - 2013 May
TI  - Osteopontin mediates macrophage chemotaxis via alpha4 and alpha9 integrins and survival 
      via the alpha4 integrin.
PG  - 1194-202
LID - 10.1002/jcb.24462 [doi]
AB  - Osteopontin (OPN) is highly expressed by macrophages and plays a key role in the 
      pathology of several chronic inflammatory diseases including atherosclerosis and 
      the foreign body reaction. However, the molecular mechanism behind OPN regulation 
      of macrophage functions is not well understood. OPN is a secreted molecule and 
      interacts with several integrins via two domains: the RGD sequence binding to 
      alpha(v) -containing integrins, and the SLAYGLR sequence binding to alpha(4) beta(1), alpha(4) 
      beta(7), and alpha(9) beta(1) integrins. Here we determined the role of OPN in macrophage 
      survival, chemotaxis, and activation state. For survival studies, OPN 
      treated-bone marrow derived macrophages (BMDMs) were challenged with growth 
      factor withdrawal and neutralizing integrin antibodies. We found that survival in 
      BMDMs is mediated primarily through the alpha(4) integrin. In chemotaxis studies, we 
      observed that migration to OPN was blocked by neutralizing alpha(4) and alpha(9) integrin 
      antibodies. Further, OPN did not affect macrophage activation as measured by 
      IL-12 production. Finally, the relative contributions of the RGD and the SLAYGLR 
      functional domains of OPN to leukocyte recruitment were evaluated in an in vivo 
      model. We generated chimeric mice expressing mutated forms of OPN in 
      myeloid-derived leukocytes, and found that the SLAYGLR functional domain of OPN, 
      but not the RGD, mediates macrophage accumulation in response to 
      thioglycollate-elicited peritonitis. Collectively, these data indicate that alpha(4) 
      and alpha(9) integrins interacting with OPN via the SLAYGLR domain play a key role in 
      macrophage biology by regulating migration, survival, and accumulation.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Lund, Susan Amanda
AU  - Lund SA
AD  - Department of Bioengineering, University of Washington, Seattle, WA 98109, USA.
FAU - Wilson, Carole L
AU  - Wilson CL
FAU - Raines, Elaine W
AU  - Raines EW
FAU - Tang, Jingjing
AU  - Tang J
FAU - Giachelli, Cecilia M
AU  - Giachelli CM
FAU - Scatena, Marta
AU  - Scatena M
LA  - eng
GR  - P01 HL018645/HL/NHLBI NIH HHS/United States
GR  - HL-018645/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Thioglycolates)
RN  - 0 (integrin alpha9)
RN  - 106441-73-0 (Osteopontin)
RN  - 143198-26-9 (Integrin alpha4)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Cell Survival
MH  - *Chemotaxis
MH  - Cytokines/biosynthesis
MH  - Inflammation Mediators/metabolism
MH  - Integrin alpha Chains/*metabolism
MH  - Integrin alpha4/*metabolism
MH  - Macrophages/*cytology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Osteopontin/chemistry/*metabolism
MH  - Peritonitis/metabolism/pathology
MH  - Phenotype
MH  - Protein Structure, Tertiary
MH  - Signal Transduction
MH  - Structure-Activity Relationship
MH  - Thioglycolates
EDAT- 2012/11/30 06:00
MHDA- 2013/08/28 06:00
CRDT- 2012/11/30 06:00
PHST- 2011/11/14 00:00 [received]
PHST- 2012/11/12 00:00 [accepted]
PHST- 2012/11/30 06:00 [entrez]
PHST- 2012/11/30 06:00 [pubmed]
PHST- 2013/08/28 06:00 [medline]
AID - 10.1002/jcb.24462 [doi]
PST - ppublish
SO  - J Cell Biochem. 2013 May;114(5):1194-202. doi: 10.1002/jcb.24462.