Proteinase 3 contributes to transendothelial migration of NB1-positive neutrophils. J Immunol 2012 Mar 01;188(5):2419-26
Date
01/24/2012Pubmed ID
22266279Pubmed Central ID
PMC3288489DOI
10.4049/jimmunol.1102540Scopus ID
2-s2.0-84857484531 (requires institutional sign-in at Scopus site) 66 CitationsAbstract
Neutrophil transmigration requires the localization of neutrophils to endothelial cell junctions, in which receptor-ligand interactions and the action of serine proteases promote leukocyte diapedesis. NB1 (CD177) is a neutrophil-expressed surface molecule that has been reported to bind proteinase 3 (PR3), a serine protease released from activated neutrophils. PR3 has demonstrated proteolytic activity on a number of substrates, including extracellular matrix proteins, although its role in neutrophil transmigration is unknown. Recently, NB1 has been shown to be a heterophilic binding partner for the endothelial cell junctional protein, PECAM-1. Disrupting the interaction between NB1 and PECAM-1 significantly inhibits neutrophil transendothelial cell migration on endothelial cell monolayers. Because NB1 interacts with endothelial cell PECAM-1 at cell junctions where transmigration occurs, we considered that NB1-PR3 interactions may play a role in aiding neutrophil diapedesis. Blocking Abs targeting the heterophilic binding domain of PECAM-1 significantly inhibited transmigration of NB1-positive neutrophils through IL-1β-stimulated endothelial cell monolayers. PR3 expression and activity were significantly increased on NB1-positive neutrophils following transmigration, whereas neutrophils lacking NB1 demonstrated no increase in PR3. Finally, using selective serine protease inhibitors, we determined that PR3 activity facilitated transmigration of NB1-positive neutrophils under both static and flow conditions. These data demonstrate that PR3 contributes in the selective recruitment of the NB1-positive neutrophil population.
Author List
Kuckleburg CJ, Tilkens SB, Santoso S, Newman PJMESH terms used to index this publication - Major topics in bold
Enzyme ActivationGPI-Linked Proteins
Gene Expression Regulation
Human Umbilical Vein Endothelial Cells
Humans
Isoantigens
Myeloblastin
Neutrophils
Receptors, Cell Surface
Transendothelial and Transepithelial Migration
