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) 58 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 PJAuthor
Peter J. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH 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