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: (View Article at PubMed) PMID:19106808
DOI: Full-text: DOI:10.1097/SHK.0b013e31819962b2

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.

Disease Annotations    
Acute Lung Injury  (IEP,IMP,ISO)

Gene Ontology Annotations    

Biological Process

Cellular Component
cell surface  (IDA)

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  (chemokine (C-X-C motif) 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