PMID- 19897576
OWN - NLM
STAT- MEDLINE
DCOM- 20100326
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 115
IP  - 7
DP  - 2010 Feb 18
TI  - Three-dimensional migration of macrophages requires Hck for podosome organization 
      and extracellular matrix proteolysis.
PG  - 1444-52
LID - 10.1182/blood-2009-04-218735 [doi]
AB  - Tissue infiltration of phagocytes exacerbates several human pathologies including 
      chronic inflammations or cancers. However, the mechanisms involved in macrophage 
      migration through interstitial tissues are poorly understood. We investigated the 
      role of Hck, a Src-family kinase involved in the organization of matrix adhesion 
      and degradation structures called podosomes. In Hck(-/-) mice submitted to 
      peritonitis, we found that macrophages accumulated in interstitial tissues and 
      barely reached the peritoneal cavity. In vitro, 3-dimensional (3D) migration and 
      matrix degradation abilities, 2 protease-dependent properties of bone 
      marrow-derived macrophages (BMDMs), were affected in Hck(-/-) BMDMs. These 
      macrophages formed few and undersized podosome rosettes and, consequently, had 
      reduced matrix proteolysis operating underneath despite normal expression and 
      activity of matrix metalloproteases. Finally, in fibroblasts unable to infiltrate 
      matrix, ectopic expression of Hck provided the gain-of-3D migration function, 
      which correlated positively with formation of podosome rosettes. In conclusion, 
      spatial organization of podosomes as large rosettes, proteolytic degradation of 
      extracellular matrix, and 3D migration appeared to be functionally linked and 
      regulated by Hck in macrophages. Hck, as the first protein combining a 
      phagocyte-limited expression with a role in 3D migration, could be a target for 
      new anti-inflammatory and antitumor molecules.
FAU - Cougoule, Celine
AU  - Cougoule C
AD  - Centre National de la Recherche Scientifique (CNRS), Institut de Pharmacologie et 
      de Biologie Structurale (IPBS), Departement Mecanismes Moleculaires des 
      Infections Mycobacteriennes, Toulouse, France.
FAU - Le Cabec, Veronique
AU  - Le Cabec V
FAU - Poincloux, Renaud
AU  - Poincloux R
FAU - Al Saati, Talal
AU  - Al Saati T
FAU - Mege, Jean-Louis
AU  - Mege JL
FAU - Tabouret, Guillaume
AU  - Tabouret G
FAU - Lowell, Clifford A
AU  - Lowell CA
FAU - Laviolette-Malirat, Nathalie
AU  - Laviolette-Malirat N
FAU - Maridonneau-Parini, Isabelle
AU  - Maridonneau-Parini I
LA  - eng
GR  - P01 AI078869/AI/NIAID NIH HHS/United States
GR  - R01 AI065495/AI/NIAID NIH HHS/United States
GR  - AI065495/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091106
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Protease Inhibitors)
RN  - EC 2.7.10.2 (Hck protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-hck)
SB  - IM
EIN - Blood. 2010 Sep 23;116(12):2195
MH  - 3T3 Cells
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Cell Movement/drug effects/*physiology
MH  - Cells, Cultured
MH  - Extracellular Matrix/drug effects/*metabolism
MH  - Imaging, Three-Dimensional
MH  - Macrophages, Peritoneal/*enzymology/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Peritoneal Cavity/pathology
MH  - Peritonitis/*metabolism/pathology
MH  - Phagocytes/metabolism/pathology
MH  - Protease Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-hck/genetics/*metabolism
PMC - PMC5070714
EDAT- 2009/11/10 06:00
MHDA- 2010/03/27 06:00
PMCR- 2010/02/18
CRDT- 2009/11/10 06:00
PHST- 2009/11/10 06:00 [entrez]
PHST- 2009/11/10 06:00 [pubmed]
PHST- 2010/03/27 06:00 [medline]
PHST- 2010/02/18 00:00 [pmc-release]
AID - S0006-4971(20)56756-6 [pii]
AID - 2009/218735 [pii]
AID - 10.1182/blood-2009-04-218735 [doi]
PST - ppublish
SO  - Blood. 2010 Feb 18;115(7):1444-52. doi: 10.1182/blood-2009-04-218735. Epub 2009 
      Nov 6.