RGD Reference Report - Infiltrated neutrophils acquire novel chemokine receptor expression and chemokine responsiveness in chronic inflammatory lung diseases. - Rat Genome Database

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Infiltrated neutrophils acquire novel chemokine receptor expression and chemokine responsiveness in chronic inflammatory lung diseases.

Authors: Hartl, D  Krauss-Etschmann, S  Koller, B  Hordijk, PL  Kuijpers, TW  Hoffmann, F  Hector, A  Eber, E  Marcos, V  Bittmann, I  Eickelberg, O  Griese, M  Roos, D 
Citation: Hartl D, etal., J Immunol. 2008 Dec 1;181(11):8053-67.
RGD ID: 4145632
Pubmed: PMID:19017998   (View Abstract at PubMed)

Various inflammatory diseases are characterized by tissue infiltration of neutrophils. Chemokines recruit and activate leukocytes, but neutrophils are traditionally known to be restricted in their chemokine receptor (CR) expression repertoire. Neutrophils undergo phenotypic and functional changes under inflammatory conditions, but the mechanisms regulating CR expression of infiltrated neutrophils at sites of chronic inflammation are poorly defined. Here we show that infiltrated neutrophils from patients with chronic inflammatory lung diseases and rheumatoid arthritis highly express CR on their surface that are absent or only marginally expressed on circulating neutrophils, i.e., CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4, as measured by flow cytometry, immunohistochemistry, and confocal microscopy. The induction of CR surface expression on infiltrated neutrophils was functionally relevant, because receptor activation by chemokine ligands ex vivo modulated neutrophil effector functions such as respiratory burst activity and bacterial killing. In vitro studies with isolated neutrophils demonstrated that the surface expression of CR was differentially induced in a cytokine-mediated, protein synthesis-dependent manner (CCR1, CCR3), through Toll-like (CXCR3) or NOD2 (CCR5) receptor engagement, through neutrophil apoptosis (CCR5, CXCR4), and/or via mobilization of intracellular CD63(+) granules (CXCR3). CR activation on infiltrated neutrophils may represent a key mechanism by which the local inflammatory microenvironment fine-tunes neutrophil effector functions in situ. Since the up-regulation of CR was exclusively found on infiltrated neutrophils at inflammatory sites in situ, the targeting of these G protein-coupled receptors may have the potential to site-specifically target neutrophilic inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  IEP 4145632protein:increased expression:respiratory system fluid/secretion and neutrophil RGD 
asthma  ISOCCR3 (Homo sapiens)4145632; 4145632protein:increased expression:respiratory system fluid/secretion and neutrophil RGD 
chronic obstructive pulmonary disease  IEP 4145632protein:increased expression:respiratory system fluid/secretion and neutrophil RGD 
chronic obstructive pulmonary disease  IEP 4145632protein:increased expression:respiratory system fluid/secretion and neutrophilRGD 
chronic obstructive pulmonary disease  ISOCCR3 (Homo sapiens)4145632; 4145632protein:increased expression:respiratory system fluid/secretion and neutrophil RGD 
chronic obstructive pulmonary disease  ISOCXCR3 (Homo sapiens)4145632; 4145632protein:increased expression:respiratory system fluid/secretion and neutrophilRGD 
cystic fibrosis  IEP 4145632protein:increased expression:respiratory system fluid/secretion and neutrophil RGD 
cystic fibrosis  IEP 4145632protein:increased expression:respiratory system fluid/secretion and neutrophilRGD 
cystic fibrosis  ISOCCR3 (Homo sapiens)4145632; 4145632protein:increased expression:respiratory system fluid/secretion and neutrophil RGD 
cystic fibrosis  ISOCXCR3 (Homo sapiens)4145632; 4145632protein:increased expression:respiratory system fluid/secretion and neutrophilRGD 
rheumatoid arthritis  IEP 4145632protein:increased expression:synovial fluid and neutrophil RGD 
rheumatoid arthritis  IEP 4145632protein:increased expression:synovial fluid and neutrophilRGD 
rheumatoid arthritis  ISOCCR3 (Homo sapiens)4145632; 4145632protein:increased expression:synovial fluid and neutrophil RGD 
rheumatoid arthritis  ISOCXCR3 (Homo sapiens)4145632; 4145632protein:increased expression:synovial fluid and neutrophilRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr3  (C-C motif chemokine receptor 3)
Cxcr3  (C-X-C motif chemokine receptor 3)

Genes (Mus musculus)
Ccr3  (C-C motif chemokine receptor 3)
Cxcr3  (C-X-C motif chemokine receptor 3)

Genes (Homo sapiens)
CCR3  (C-C motif chemokine receptor 3)
CXCR3  (C-X-C motif chemokine receptor 3)


Additional Information