Acute lung injury (ALI) is the injury of alveolar epithelial cells and capillary endothelial
cells caused by various factors. Complement system and pyroptosis have been proved to be
involved in ALI, and inhibition of C5a/C5a receptor (C5aR) could alleviate ALI. This study aimed
to investigate whether C5a/C5aR inhibition could protect against LPS-induced ALI via mediating
pyroptosis. Rats were assigned into four groups: Control, LPS, LPS+W-54011 1mg/kg, and
LPS+W-54011 5mg/kg. Beas-2B cells pretreated with or without C5a and W-54011, alone and in
combination, were challenged with LPS+ATP. Results unveiled that LPS caused lung tissue injury
and inflammatory response, increased pyroptotic and apoptotic factors, along with elevated C5a
concentration and C5aR expressions. However, W-54011 pretreatment alleviated lung damage and
pulmonary edema, reduced inflammation and prevented cell pyroptosis. In vitro studies
confirmed
that LPS+ATP reduced cell viability, promoted cell death, generated inflammatory factors and
promoted expressions of pyroptosis-related proteins, which could be prevented by W-54011
pretreatment while intensified by C5a pretreatment. The co-treatment of C5a and W-54011 could
blunt the effects of C5a on LPS+ATP-induced cytotoxicity. In conclusion, inhibition of C5a/C5aR
developed protective effects against LPS-induced ALI and the cytotoxicity of Beas-2B cells, and
these effects may depend on blocking pyroptosis.
Keywords: C5a; acute lung injury; complement; inflammation; pyroptosis.
Reference
Wang, R., Wang, Y., Hu, L., Lu, Z., & Wang, X. (2021). Inhibition of complement C5a receptor protects lung cells and tissues against lipopolysaccharide-induced injury via blocking pyroptosis. Aging (Albany NY), 13(6), 8588.