摘要
Neutrophils play an essential role in the innate immune response to infection. Neutrophils migrate from the vasculature into the tissue in response to infection. Recently, a neutrophil cell surface receptor, CD177, was shown to help mediate neutrophil migration across the endothelium through interactions with PECAMI. We examined a publicly available gene array dataset of CD177 expression from human neutrophils following pulmonary endotoxin instillation. Among all 22,214 genes examined, CD177 mRNA was the most upregu- lated following endotoxin exposure. The high level of CD177 expression is also maintained in airspace neu- trophils, suggesting a potential involvement of CD177 in neutrophil infiltration under infectious diseases. To determine the role of CD177 in neutrophils in vivo, we constructed a CD177-genetic knockout mouse model. The mice with homozygous deletion of CD177 have no discernible phenotype and no significant change in immune cells, other than decreased neutrophil counts in peripheral blood. We examined the role of CD177 in neutrophil accumulation using a skin infection model with Staphylococcus aureus. CD177 deletion reducedneutrophil counts in inflammatory skin caused by S. aureus. Mechanistically we found that CD177 deletion in mouse neutrophils has no significant impact in CXCLI/ KC- or fMLP-induced migration, but led to significant cell death. Herein we established a novel genetic mouse model to study the role of CD177 and found that CD177 plays an important role in neutrophils.
Neutrophils play an essential role in the innate immune response to infection. Neutrophils migrate from the vasculature into the tissue in response to infection. Recently, a neutrophil cell surface receptor, CD177, was shown to help mediate neutrophil migration across the endothelium through interactions with PECAMI. We examined a publicly available gene array dataset of CD177 expression from human neutrophils following pulmonary endotoxin instillation. Among all 22,214 genes examined, CD177 mRNA was the most upregu- lated following endotoxin exposure. The high level of CD177 expression is also maintained in airspace neu- trophils, suggesting a potential involvement of CD177 in neutrophil infiltration under infectious diseases. To determine the role of CD177 in neutrophils in vivo, we constructed a CD177-genetic knockout mouse model. The mice with homozygous deletion of CD177 have no discernible phenotype and no significant change in immune cells, other than decreased neutrophil counts in peripheral blood. We examined the role of CD177 in neutrophil accumulation using a skin infection model with Staphylococcus aureus. CD177 deletion reducedneutrophil counts in inflammatory skin caused by S. aureus. Mechanistically we found that CD177 deletion in mouse neutrophils has no significant impact in CXCLI/ KC- or fMLP-induced migration, but led to significant cell death. Herein we established a novel genetic mouse model to study the role of CD177 and found that CD177 plays an important role in neutrophils.
基金
We sincerely thank Drs. Tang and Coldren for sharing the microarray datasets. The CD177 mouse strain used for this research project was created from an ES cell clone （12120a-B11） obtained from the KOMP Repository （www.komp.org） and generated by Regeneron Pharmaceuticals, Inc. This work was supported by NIH grant CA158055 （W.Z.） and NIH T32 GM007337 （N.B.）. Additionally, W.Z. was supported by depart- mental start up funds, and seed grants from the Department of Pathology at the University of Iowa Carver College of Medicine and from the American Cancer Society. G.H.L. was supported by the National Basic Research Program （973 Program） （Nos. 2015CB964800 and 2014CB964600）, the Strategic Priority Research Program of the Chi- nese Academy of Sciences （XDA01020312）, the National Natural Science Foundation of China （Grant Nos. 81271266, 31222039, 81330008, 31201111, and 81300677）, Beijing Natural Science Foun- dation （7141005）, and the Thousand Young Talents program of China, and State Key Laboratory of Drug Research （SIMM1302KF-17）. Q.X. was supported by a scholarship from the China Scholarship Council.
