RGD Reference Report - Delay of LPS-induced acute lung injury resolution by soluble immune complexes is neutrophil dependent. - Rat Genome Database

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Delay of LPS-induced acute lung injury resolution by soluble immune complexes is neutrophil dependent.

Authors: Wu, CL  Lin, LY  Yeh, HM  Chan, MC  Yang, CH  Hsueh, CM 
Citation: Wu CL, etal., Shock. 2009 Sep;32(3):276-85.
RGD ID: 5147925
Pubmed: PMID:19106808   (View Abstract at PubMed)
DOI: DOI:10.1097/SHK.0b013e31819962b2   (Journal Full-text)

The pathophysiological role of soluble immune complexes (SICXs) and its relationship with neutrophils were investigated in LPS-induced acute lung injury (ALI) animal model (Sprague-Dawley rat) and through the in vitro studies. Results showed that LPS-induced SICX was timely related to changes of tumor necrosis factor alpha and macrophage inflammatory protein 2 (inflammatory cytokines) in bronchoalveolar lavage fluid. In vitro study showed that SICX can bind to Fc gammaR (CD64 and CD32 or CD16) to prevent the apoptosis of neutrophils. The SICX-mediated apoptosis inhibition was extracellular signal-regulated kinase (ERK) or phosphoinositide 3 kinase dependent and was interrupted by PD98059 and LY294002. In vivo, additional amount of SICX exacerbated the lung injury caused by LPS. LPS-induced lung injury and macrophage inflammatory protein 2 release, however, were prevented by CD64 and CD32 blockers (decoy antibodies). In conclusion, excessive amount of SICX in lung can act through Fc gammaRs to protect bronchoalveolar lavage fluid neutrophils from apoptosis that eventually lead to delayed resolution of ALI caused by LPS. Blockade of SICX engagement of CD32 and CD64 (with decoy antibodies) could interrupt SICX-mediated protection of neutrophils and protect lung from LPS-induced injury. The decoy antibodies may therefore have therapeutic utility in ALI.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCL2HumanAcute Lung Injury  ISOCxcl2 (Rattus norvegicus)protein:increased expression:respiratory system fluid/secretionRGD 
Cxcl2RatAcute Lung Injury  IEP protein:increased expression:respiratory system fluid/secretionRGD 
Cxcl2MouseAcute Lung Injury  ISOCxcl2 (Rattus norvegicus)protein:increased expression:respiratory system fluid/secretionRGD 
FCGR1AHumanAcute Lung Injury  ISOFcgr1a (Rattus norvegicus) RGD 
FCGR2AHumanAcute Lung Injury  ISOFcgr2a (Rattus norvegicus) RGD 
FCGR2BHumanAcute Lung Injury treatmentISOFcgr2b (Rattus norvegicus) RGD 
Fcgr1MouseAcute Lung Injury  ISOFcgr1a (Rattus norvegicus) RGD 
Fcgr1aRatAcute Lung Injury  IMP  RGD 
Fcgr2aRatAcute Lung Injury  IMP  RGD 
Fcgr2bRatAcute Lung Injury treatmentIMP  RGD 
Fcgr2bMouseAcute Lung Injury treatmentISOFcgr2b (Rattus norvegicus) RGD 
TNFHumanAcute Lung Injury  ISOTnf (Rattus norvegicus)protein:increased expression:respiratory system fluid/secretionRGD 
TnfRatAcute Lung Injury  IEP protein:increased expression:respiratory system fluid/secretionRGD 
TnfMouseAcute Lung Injury  ISOTnf (Rattus norvegicus)protein:increased expression:respiratory system fluid/secretionRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fcgr2bRatcellular response to lipopolysaccharide  IEP  RGD 
Fcgr3aRatcellular response to lipopolysaccharide  IDA  RGD 
Fcgr2bRatnegative regulation of neutrophil apoptotic process  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fcgr3aRatcell surface  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcl2  (C-X-C motif chemokine ligand 2)
Fcgr1a  (Fc gamma receptor 1A)
Fcgr2a  (Fc gamma receptor 2A)
Fcgr2b  (Fc gamma receptor 2B)
Fcgr3a  (Fc gamma receptor 3A)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Cxcl2  (C-X-C motif chemokine ligand 2)
Fcgr1  (Fc receptor, IgG, high affinity I)
Fcgr2b  (Fc receptor, IgG, low affinity IIb)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
CXCL2  (C-X-C motif chemokine ligand 2)
FCGR1A  (Fc gamma receptor Ia)
FCGR2A  (Fc gamma receptor IIa)
FCGR2B  (Fc gamma receptor IIb)
TNF  (tumor necrosis factor)


Additional Information