Anti-human platelet antigen (HPA)-1a antibodies may affect trophoblast functions crucial for placental development: A laboratory study using an in vitro model
| Autor: | Anne Husebekk, Gøril Heide, Yan Zhou, Mette Kjaer, Heidi Tiller, Inigo Martinez-Zubiaurre, Nora Hersoug Nedberg, Mariana Eksteen, Tor B. Stuge, Bjørn Skogen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Trophoblast cells Fibrinogen receptor Placenta Fetal and neonatal alloimmune thrombocytopenia 030204 cardiovascular system & hematology Epitope αVβ3 0302 clinical medicine Endocrinology Cell Movement Pregnancy lcsh:Reproduction Cell Line Transformed Alloimmunization Integrin beta3 Obstetrics and Gynecology Trophoblasts VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Endocrinology: 774 medicine.anatomical_structure Neonatal alloimmune thrombocytopenia Female Antibody VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Endokrinologi: 774 Protein Binding endocrine system lcsh:QH471-489 medicine.drug_class Integrin Biology Monoclonal antibody lcsh:Gynecology and obstetrics Andrology 03 medical and health sciences Antigen HPA-1a medicine Cell Adhesion Humans Antigens Human Platelet lcsh:RG1-991 Autoantibodies Research Placental development Trophoblast medicine.disease 030104 developmental biology Reproductive Medicine Immunology biology.protein Anti-HPA-1a antibodies Vitronectin receptor Developmental Biology |
| Zdroj: | Reproductive Biology and Endocrinology : RB&E Reproductive Biology and Endocrinology, Vol 15, Iss 1, Pp 1-8 (2017) |
| Popis: | Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies. The HPA-1a epitope is located on integrin β 3 that is associated with integrin α IIb (the fibrinogen receptor) on platelets and megakaryocytes. Integrin β 3 is also associated with integrin α V forming the α V β 3 integrin heterodimer, the vitronectin receptor, which is expressed on various cell types, including trophoblast cells. It is therefore thinkable that maternal anti-HPA-1a antibodies present during early pregnancy may affect placenta function through binding to the HPA-1a antigen epitope on invasive throphoblasts. The aim of the study was to examine whether interaction of a human anti-HPA-1a monoclonal antibody (mAb) with HPA-1a on trophoblast cells affect adhesion, migration and invasion of extravillous trophoblast cells. Methods: An in vitro model with human anti-HPA-1a mAb, clone 26.4, and the first trimester extravillous trophoblast cell line HTR8/SVneo was employed. The xCELLigence system was utilized to assess the possible effect of anti-HPA-1a mAb on adhesion and migration of HTR8/SVneo cells. Specially designed chambers precoated with Matrigel were used to assess the effect on the invasive capacity of cells. Results: We found that human anti-HPA-1a mAb 26.4 partia lly inhibits adhesion and migratory capacity of HTR8/SVneo cells. Conclusions: Our findings suggest that anti-HPA-1a antibodies may affect trophoblast functions crucial for normal placental development. Future studies including primary throphoblast cells and polyclonal anti-HPA-1a antibodies are needed to confirm these results. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|