Faculty Collaboration Database

Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1. J Immunol 2010 Apr 01;184(7):3889-96

Date

03/03/2010

Pubmed ID

20194726

Pubmed Central ID

PMC4154536

DOI

10.4049/jimmunol.0903136

Scopus ID

2-s2.0-77951632493 (requires institutional sign-in at Scopus site)   58 Citations

Abstract

The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S(536)N single nucleotide polymorphism of two major isoforms V(98)N(536)G(643) and L(98)S(536)R(643) and a yet-to-be-determined region on CD177. In vitro transendothelial migration experiments revealed that CD177(+) neutrophils migrated significantly faster through HUVECs expressing the LSR, compared with the VNG, allelic variant of PECAM-1 and that this correlated with the decreased ability of anti-PECAM-1 Ab of ITIM tyrosine phosphorylation in HUVECs expressing the LSR allelic variant relative to the VNG allelic variant. Moreover, engagement of PECAM-1 with rCD177-Fc (to mimic heterophilic CD177 binding) suppressed Ab-induced tyrosine phosphorylation to a greater extent in cells expressing the LSR isoform compared with the VNG isoform, with a corresponding increased higher level of beta-catenin phosphorylation. These data suggest that heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner.

Author List

Bayat B, Werth S, Sachs UJ, Newman DK, Newman PJ, Santoso S

Authors

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Base Sequence
Cell Separation
Endothelial Cells
Flow Cytometry
GPI-Linked Proteins
Humans
Immunoblotting
Isoantigens
Membrane Glycoproteins
Molecular Sequence Data
Neutrophil Infiltration
Neutrophils
Platelet Endothelial Cell Adhesion Molecule-1
Polymorphism, Single Nucleotide
Protein Isoforms
RNA, Messenger
Receptors, Cell Surface
Reverse Transcriptase Polymerase Chain Reaction
Surface Plasmon Resonance