The abortion-prone mating combination CBA/J × DBA/2 has been recognized as a model of preeclampsia, and complement activation has been implicated in the high rate of pregnancy loss observed in CBA/J mice. We have analyzed the implantation sites collected from DBA/2-mated CBA/J mice for the deposition of the complement recognition molecules using CBA/J mated with BALB/c mice as a control group. MBL-A was observed in the implantation sites of CBA/J × DBA/2 combination in the absence of MBL-C and was undetectable in BALB/c-mated CBA/J mice. Conversely, C1q was present in both mating combinations. Searching for other complement components localized at the implantation sites of CBA/J × DBA/2, we found C4 and C3, but we failed to reveal C1r. These data suggest that complement is activated through the lectin pathway and proceeds to completion of the activation sequence as revealed by C9 deposition. MBL-A was detected as early as 3.5 d of pregnancy, and MBL-A deficiency prevented pregnancy loss in the abortion-prone mating combination. The contribution of the terminal complex to miscarriage was supported by the finding that pregnancy failure was largely inhibited by the administration of neutralizing Ab to C5. Treatment of DBA/2-mated CBA/J mice with Polyman2 that binds to MBL-A with high affinity proved to be highly effective in controlling the activation of the lectin pathway and in preventing fetal loss.
Critical role and therapeutic control of the lectin pathway of complement activation in an abortion-prone mouse mating / M. Petitbarat, P. Durigutto, P. Macor, R. Bulla, A. Palmioli, A. Bernardi, M. De Simoni, N. Ledee, G. Chaouat, F. Tedesco. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 195:12(2015 Dec 15), pp. 5602-5607.
|Titolo:||Critical role and therapeutic control of the lectin pathway of complement activation in an abortion-prone mouse mating|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||15-dic-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.4049/jimmunol.1501361|
|Appare nelle tipologie:||01 - Articolo su periodico|