Complement is an important player of the inflammatory process associated with pre-eclampsia (PE) as suggested by the finding reported by several groups that complement activation products are present both in the circulation and at tissue level in PE patients. We now present data showing that activators of the classical and lectin pathways play a different role in inducing local changes in PE placentae. Immunohistochemical analysis of placental tissue revealed deposition of C1q and MBL on endothelial cells and stroma in normal placentae, The distribution of C1q and MBL was essentially similar in PE placentae, but the staining intensity was definitely stronger. Failure to detect C1s excluded complement activation through the classical pathway, while the presence of C4 and C3 was compatible with the activation of the lectin pathway. Deposits of C9 in the basal plate enriched in fibrinoid material and in the subendothelium of vessels, particularly in those undergoing acute atherosis, were observed in PE placentae. The pathogenic role of the lectin pathway of complement activation in PE was investigated using the CBA/J x DBA/2 mouse model of PE characterized by recurrent miscarriages. Pregnancy loss was found to be associated with an early localization of MBL-A, but not of MBL-C, at embryo implantation sites followed by deposition of C4, C3 and C9. C1q was also detected at the same sites in the absence of C1s ruling out its involvement in the classical pathway activation. To determine the contribution of MBL-A to embryo resorption, we generated female MBL-A -/- CBA/J mice that were mated to DBA/2 male mice. This mating combination resulted in a significant decrease in the miscarriage rate. Similar results were obtained treating MBL-A +/+ CBA/J female mice pregnant by DBA/2 male mice with Polyman2, a mannosylated molecule known to bind to MBL-A and to control brain ischemic injury. We have previously shown that extravillous trophoblasts invading the decidua and surrounding remodelled spiral arteries synthesize C1q and that C1q-/- mice, like PE patients, fail to remodel these vessels. Data will be presented indicating that this pathological situation can be reversed by mating C1q +/+ male mice with C1q -/- female mice. Under this condition the vessels are to a large extent remodelled and are surrounded by trophoblasts expressing C1q.

Dual role of the complement system in pre-eclampsia

BULLA, ROBERTA;
2015

Abstract

Complement is an important player of the inflammatory process associated with pre-eclampsia (PE) as suggested by the finding reported by several groups that complement activation products are present both in the circulation and at tissue level in PE patients. We now present data showing that activators of the classical and lectin pathways play a different role in inducing local changes in PE placentae. Immunohistochemical analysis of placental tissue revealed deposition of C1q and MBL on endothelial cells and stroma in normal placentae, The distribution of C1q and MBL was essentially similar in PE placentae, but the staining intensity was definitely stronger. Failure to detect C1s excluded complement activation through the classical pathway, while the presence of C4 and C3 was compatible with the activation of the lectin pathway. Deposits of C9 in the basal plate enriched in fibrinoid material and in the subendothelium of vessels, particularly in those undergoing acute atherosis, were observed in PE placentae. The pathogenic role of the lectin pathway of complement activation in PE was investigated using the CBA/J x DBA/2 mouse model of PE characterized by recurrent miscarriages. Pregnancy loss was found to be associated with an early localization of MBL-A, but not of MBL-C, at embryo implantation sites followed by deposition of C4, C3 and C9. C1q was also detected at the same sites in the absence of C1s ruling out its involvement in the classical pathway activation. To determine the contribution of MBL-A to embryo resorption, we generated female MBL-A -/- CBA/J mice that were mated to DBA/2 male mice. This mating combination resulted in a significant decrease in the miscarriage rate. Similar results were obtained treating MBL-A +/+ CBA/J female mice pregnant by DBA/2 male mice with Polyman2, a mannosylated molecule known to bind to MBL-A and to control brain ischemic injury. We have previously shown that extravillous trophoblasts invading the decidua and surrounding remodelled spiral arteries synthesize C1q and that C1q-/- mice, like PE patients, fail to remodel these vessels. Data will be presented indicating that this pathological situation can be reversed by mating C1q +/+ male mice with C1q -/- female mice. Under this condition the vessels are to a large extent remodelled and are surrounded by trophoblasts expressing C1q.
http://www.sciencedirect.com/science/journal/01615890/67/1
File in questo prodotto:
File Dimensione Formato  
Dual role of the complement system in pre-eclampsia.pdf

non disponibili

Descrizione: PDF versione editoriale
Tipologia: Documento in Versione Editoriale
Licenza: Digital Rights Management non definito
Dimensione 1.71 MB
Formato Adobe PDF
1.71 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2887750
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 0
social impact