Anti-P- and E-selectin therapy prevents abortion in the CBA/J x DBA/2J combination by blocking the migration of Th1 lymphocytes into the foetal-maternal interface.
Leukocyte migration into inflamed tissues comprises dynamic interactions between immune and endothelial cells through events controlled by adhesion molecules, e.g., P- and E-selectins, which mediate Th1 cells recruitment after injury. Since miscarriage is known to be a Th1 event and selectins are expressed at the murine foetal-maternal interface, the purpose of our study was to investigate whether blocking P- and E-selectins before implantation could inhibit Th1 migration into the foetal-maternal interface and thus prevent foetal rejection. DBA/2J-mated CBA/J females were treated with monoclonal antibodies (mAbs) against P-selectin or with both, anti-P- and anti-E-selectins combined on days 2 and 4 of pregnancy. PBS-treated females served as controls. Our data revealed a significant improvement in pregnancy outcome in both treated groups compared to the control, which is due to the effectiveness of the mAb against P-selectin, since the treatment with anti-E-selectin alone could not prevent abortion. We further observed that there was diminished Th1 cytokine production by decidual immune cells in all treated groups in comparison to the controls. Our data first confirm the important role of P-selectin in mediating the extravasation of abortive cells, while opening new therapeutic opportunities.
Institute of Medical Immunology, Charité, Medical University of Berlin, Berlin, Germany.
Annarosa Zambon
AZ
Bertoja
Maria Laura
ML
Zenclussen
Pablo Ariel
PA
Casalis
André
A
Sollwedel
Anne
A
Schumacher
Christian
C
Woiciechowsky
Hans-Dieter
HD
Volk
Ana Claudia
AC
Zenclussen
D000022:Abortion, Spontaneous / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis; D003656:Decidua / Q000378:metabolism; D019040:E-Selectin / Q000276:immunology*; D005260:Female; D007167:Immunotherapy; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D019007:P-Selectin / Q000276:immunology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D018417:Th1 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D019040:E-Selectin; D019007:P-Selectin