PMID- 20017911
OWN - NLM
STAT- MEDLINE
DCOM- 20100311
LR  - 20211020
IS  - 1741-7007 (Electronic)
IS  - 1741-7007 (Linking)
VI  - 7
DP  - 2009 Dec 17
TI  - The obesity and inflammatory marker haptoglobin attracts monocytes via 
      interaction with chemokine (C-C motif) receptor 2 (CCR2).
PG  - 87
LID - 10.1186/1741-7007-7-87 [doi]
AB  - BACKGROUND: Obesity is a chronic low inflammatory state. In the obesity condition 
      the white adipose tissue (WAT) is massively infiltrated with 
      monocytes/macrophages, and the nature of the signals recruiting these 
      inflammatory cells has yet to be fully elucidated. Haptoglobin (Hp) is an 
      inflammatory marker and its expression is induced in the WAT of obese subjects. 
      In an effort to elucidate the biological significance of Hp presence in the WAT 
      and of its upregulation in obesity we formulated the hypothesis that Hp may serve 
      as a macrophage chemoattractant. RESULTS: We demonstrated by chemotaxis assay 
      that Hp is able to attract chemokine (C-C motif) receptor 2 (CCR2)-transfected 
      pre-B lymphocytes and monocytes in a dose-dependent manner. Moreover, Hp-mediated 
      migration of monocytes is impaired by CCR2-specific inhibition or previous cell 
      exposure to monocyte chemoattractant protein 1 (MCP1) (also known as CCR2 ligand 
      or chemokine (C-C motif) ligand 2 (CCL2)). Downstream effects of Hp/CCR2 
      interaction were also investigated: flow cytometry proved that monocytes treated 
      with Hp show reduced CCR2 expression on their surface; Hp interaction induces 
      calcium release that is reduced upon pretreatment with CCR2 antagonist; 
      extracellular signal-regulated kinase (ERK)1/2, a signal transducer activated by 
      CCR2, is phosphorylated following Hp treatment and this phosphorylation is 
      reduced when cells are pretreated with a specific CCR2 inhibitor. Consistently, 
      blocking the ERK1/2 pathway with U0126, the selective inhibitor of the ERK 
      upstream mitogen-activated protein (MAP)-ERK kinase (MEK), results in a dramatic 
      reduction (by almost 100%) of the capability of Hp to induce monocyte migration. 
      CONCLUSIONS: Our data show that Hp is a novel monocyte chemoattractant and that 
      its chemotactic potential is mediated, at least in part. by its interaction with 
      CCR2.
FAU - Maffei, Margherita
AU  - Maffei M
AD  - Dulbecco Telethon Institute, CNR, Area della Ricerca di Pisa, Pisa, Italy. 
      maffeim@immr.med.unipi.it
FAU - Funicello, Marcella
AU  - Funicello M
FAU - Vottari, Teresa
AU  - Vottari T
FAU - Gamucci, Olimpia
AU  - Gamucci O
FAU - Costa, Mario
AU  - Costa M
FAU - Lisi, Simonetta
AU  - Lisi S
FAU - Viegi, Alessandro
AU  - Viegi A
FAU - Ciampi, Osele
AU  - Ciampi O
FAU - Bardi, Giuseppe
AU  - Bardi G
FAU - Vitti, Paolo
AU  - Vitti P
FAU - Pinchera, Aldo
AU  - Pinchera A
FAU - Santini, Ferruccio
AU  - Santini F
LA  - eng
GR  - TCR07007/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091217
PL  - England
TA  - BMC Biol
JT  - BMC biology
JID - 101190720
RN  - 0 (Butadienes)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HP protein, human)
RN  - 0 (Haptoglobins)
RN  - 0 (Nitriles)
RN  - 0 (Receptors, CCR2)
RN  - 0 (U 0126)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adult
MH  - B-Lymphocytes/drug effects/physiology
MH  - Butadienes/pharmacology
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cell Membrane/drug effects/physiology
MH  - Cell Movement/drug effects/physiology
MH  - Chemokine CCL2/metabolism
MH  - Chemotaxis/drug effects/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Haptoglobins/*metabolism
MH  - Humans
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism
MH  - Monocytes/drug effects/*physiology
MH  - Nitriles/pharmacology
MH  - Phosphorylation/drug effects
MH  - Receptors, CCR2/agonists/antagonists & inhibitors/*metabolism
MH  - U937 Cells
MH  - Young Adult
PMC - PMC2809058
EDAT- 2009/12/19 06:00
MHDA- 2010/03/12 06:00
PMCR- 2009/12/17
CRDT- 2009/12/19 06:00
PHST- 2009/11/27 00:00 [received]
PHST- 2009/12/17 00:00 [accepted]
PHST- 2009/12/19 06:00 [entrez]
PHST- 2009/12/19 06:00 [pubmed]
PHST- 2010/03/12 06:00 [medline]
PHST- 2009/12/17 00:00 [pmc-release]
AID - 1741-7007-7-87 [pii]
AID - 10.1186/1741-7007-7-87 [doi]
PST - epublish
SO  - BMC Biol. 2009 Dec 17;7:87. doi: 10.1186/1741-7007-7-87.