CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation

Abstract

CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with β2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1), suggesting a role in neutrophil migration. However, CD177 neutrophils exhibit no clear migratory advantage in vivo, despite interruption of in vitro transendothelial migration by CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177 and CD177 neutrophils migrated comparably. CD177 ligation selectively impaired migration of CD177 neutrophils, an effect mediated through immobilization and cellular spreading on the transwell membrane. Correspondingly, CD177 ligation enhanced its interaction with β2 integrins, as revealed by fluorescence lifetime imaging microscopy, leading to integrin-mediated phosphorylation of Src and extracellular signal-regulated kinase (ERK). CD177-driven cell activation enhanced surface β2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. We conclude that CD177 signals in a β2 integrin-dependent manner to orchestrate a set of activation-mediated mechanisms that impair human neutrophil migration.

Characterization and comparison of neutrophil extracellular traps in gingival samples of periodontitis and gingivitis: A pilot study

“…CD177 is expressed in neutrophils specifically and is upregulated during inflammation. CD177 + neutrophils represent functionally activated population and CD177 signals in a β2 integrin‐dependent manner to orchestrate a set of activation‐mediated mechanisms that impair human neutrophil migration . Previous studies have used CD177 as a specific neutrophil marker for the characterization of NETs, including studies on supragingival biofilms …”

Neutrophil phenotypes in health and disease

“…Between 45 and 65% of circulating neutrophils are CD177‐positive . CD177 is a glycoprotein‐anchored receptor that among other functions regulates transmigration of neutrophils through binding of platelet endothelial cell adhesion molecule‐1 . CD177‐positive neutrophils seem to play a role in the pathogenesis of ANCA‐associated vasculitis.…”

Human CD31 on porcine cells suppress xenogeneic neutrophil‐mediated cytotoxicity via the inhibition of NETosis

“…Furthermore, the function of heterophilic ligands of CD31 such as CD177 glycosaminoglycans in xenogeneic rejection is also need to be determined. Bai et al reported the suppressive function in neutrophil migration. However, the function of CD177 in neutrophil‐mediated cytotoxicity and NETosis is still unknown.…”