title: Characterization of a novel mouse model with genetic deletion of CD177.
abstract: 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 PECAM1. 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 upregulated following endotoxin exposure. The high level of CD177 expression is also maintained in airspace neutrophils, 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 reduced neutrophil counts in inflammatory skin caused by S. aureus. Mechanistically we found that CD177 deletion in mouse neutrophils has no significant impact in CXCL1/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.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Julia
authors.initials: J
authors.lastname: Klesney-Tait
authors.forename: Kathy
authors.initials: K
authors.lastname: Keck
authors.forename: Corey
authors.initials: C
authors.lastname: Parlet
authors.forename: Nicholas
authors.initials: N
authors.lastname: Borcherding
authors.forename: Ryan
authors.initials: R
authors.lastname: Kolb
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Lorraine
authors.initials: L
authors.lastname: Tygrett
authors.forename: Thomas
authors.initials: T
authors.lastname: Waldschmidt
authors.forename: Alicia
authors.initials: A
authors.lastname: Olivier
authors.forename: Songhai
authors.initials: S
authors.lastname: Chen
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Liu
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Li
authors.forename: Weizhou
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007249:Inflammation / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D007519:Isoantigens / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D013211:Staphylococcus aureus / Q000472:pathogenicity; D015533:Transcriptional Activation
chemical_list: C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D007519:Isoantigens; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface