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)   67 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

Author

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter 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