Critical Role Of Class A Scavenger Receptor In Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease(COPD)is a disease characterized by irreversible and progressive airflow limitation induced by long-term inflammation.Alveolar macrophages(AM)have been identified as the main cell type that plays an important role in the pathophysiology of COPD.Macrophages lead to secretion of chemotactic factors and could markedly increase after exposure to cigarette smoke.The ability of AMs to clear respiratory pathogens and apoptotic cells has been impaired in COPD,which might play a key role in pathogenesis.Class a scavenger receptor(SR-A)locates on the surface of alveolar macrophages and is attributed to an impressively wide range of functions,involving phagocytosis,antigen presentation,apoptotic cell clearance,and bacterial and particle uptake.Once triggered,it will initiate a signaling cascade that leads to activation and nuclear translocation of the transcription factors.This process activates intracellular signaling pathways and reach the zenith after releasing pro-inflammatory cytokines.We speculate that SR-A might be associated with pathogenesis and exacerbation of COPD.In the first part of our experiment,we investigate the relationship between the variants of SR-A and chronic obstructive pulmonary disease(COPD)with or without lung cancer in China.100 patients with COPD with lung cancer,100 patients with COPD without lung cancer,and 100 healthy smokers were enrolled for genotyping of single-nucleotide polymorphisms(SNP)by gene sequencing.The variant rs13306550 found in the splice donor site was a risk factor for COPD susceptibility,but had little influence on severity of COPD and pathogenesis of lung cancer in patients with COPD.In the second part of this study,to investigate role of SR-A in COPD progression,we measured SR-A expression in COPD patients and control subjects.In COPD patients,SR-A expression level was up-regulated.To further prove our hypothesis,we treated RAW264.7 cells that overexpress SR-A with lipopolysaccharides(LPS),poly(I:C),cigarette smoke extract(CSE)and H1N1 influenza.Level of inflammatory cytokines was significantly higher in RAW cell that overexpress SR-A when compared with control ones.As a result,combination of SR-A with CSE,bacteria and virus might induce inflammation and lead to long-term inflammation in COPD.In conclusion,SR-A SNP rs13306550 is associated with genetic susceptibility to COPD.Level of SR-A significantly increased in COPD patients and it could play a critical role in long-term inflammation in COPD.However,the specific mechanisms remain to be uncovered.SR-A might suggest a new therapeutic target for COPD treatment.