Formyl peptide receptor ligands promote wound closure in lung epithelial cells.
Mitochondrial antigens released from damaged cells act as "danger signals" capable of promoting innate immune cell migration and activation via formyl peptide receptors (FPRs). Lung epithelial cells are equipped to migrate and mount innate immune responses in the context of acute lung injury. The goal of this study was to determine whether lung epithelial cells express FPRs, which are capable of responding to mitochondrial antigens to promote wound closure and inflammation. Using human Beas2B lung epithelial cells grown to confluency and subjected to linear scratch injury, it was found that mitochondrial antigens enhanced epithelial wound closure, and this phenomenon was inhibited by cyclosporin H, a selective inhibitor of FPR. Although mitochondrial antigens also promoted IL-8 release, this release was not FPR dependent and was unrelated to FPR-induced lung epithelial cell wound closure. The expression of functional FPR was confirmed in Beas2B and primary human tracheobronchial epithelial cells, particularly in lamellipodia at the leading edge of the closing wound. The expression of FPR was increased in response to TNF-α, LPS, scratch injury, and mitochondrial antigen treatment. Considered together, these data confirm that human lung epithelial cells express functional FPRs, which are capable of responding to endogenous mitochondrial danger signals, to promote wound closure.
Shao
Guohong
G
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH 43210-1252, USA.
Julian
Mark W
MW
Bao
Shengying
S
McCullers
Meghan K
MK
Lai
Ju-Ping
JP
Knoell
Daren L
DL
Crouser
Elliott D
ED
D000941:Antigens / Q000737:chemistry; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000473:pathology*; D008856:Microscopy, Fluorescence / Q000379:methods; D008928:Mitochondria / Q000473:pathology; D009336:Necrosis / Q000473:pathology; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014945:Wound Healing
D000941:Antigens; D016209:Interleukin-8; D008024:Ligands; D044042:Receptors, Formyl Peptide