HPA-1a alloantibodies reduce endothelial cell spreading and monolayer integrity.

Abstract

Maternal human platelet antigen (HPA)-1a alloantibodies causing neonatal alloimmune thrombocytopenia can bind also to endothelium, via the beta3-integrin (CD61). The aim of this study was to investigate the effect of HPA-1a Abs on endothelial cell function, with emphasis on monolayer integrity. We used a CD61 mAb as a model for the HPA-1a alloantibodies and confirmed the results with purified IgG fractions from HPA-1a alloimmunized women. The effect of these antibodies was examined by monitoring the adhesion, spreading, and monolayer integrity of primary HUVECs with conventional adhesion assays as well as electrical cell-substrate impedance sensing. We found that both the mAb CD61 and the HPA-1a antibodies caused a significant reduction in HUVEC spreading. Moreover, addition of the mAb CD61 and the HPA-1a antibodies prior to or following formation of a stable endothelial monolayer negatively affected endothelial monolayer integrity, which was accompanied by a redistribution of junctional proteins. Our data suggest that HPA-1a alloantibodies have a direct effect on endothelial cell spreading and monolayer integrity, which could contribute to the increased bleeding tendency in children with neonatal alloimmune thrombocytopenia.

• Authors: Janine M van Gils, Janine Stutterheim, Trynette J van Duijn, Jaap Jan Zwaginga, Leendert Porcelijn, Masja de Haas, Peter L Hordijk
• Journal: Molecular immunology (Mol Immunol) Vol. 46 Issue 3 Pg. 406-15 (Jan 2009) ISSN: 0161-5890 [Print] England
• PMID: 19038456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Antigens, CD
• Antigens, Human Platelet
• Cadherins
• ITGB3 protein, human
• Integrin beta3
• Isoantibodies
• cadherin 5

Topics

• Antibodies (pharmacology)
• Antigens, CD (metabolism)
• Antigens, Human Platelet (immunology)
• Cadherins (metabolism)
• Cell Adhesion (drug effects)
• Cell Membrane Permeability (drug effects)
• Cell Movement (drug effects)
• Electric Impedance
• Endothelial Cells (cytology, drug effects)
• Female
• Humans
• Integrin beta3
• Isoantibodies (immunology)
• Umbilical Cord (cytology)
• Wound Healing (drug effects)