title: Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating.
abstract: 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.
authors.affiliation: MatriceLAB Innove, Hôpital Saint Louis, 75010 Paris, France;
authors.forename: Marie
authors.identifier: http://orcid.org/0000-0002-0112-983X
authors.initials: M
authors.lastname: Petitbarat
authors.affiliation: Department of Life Sciences, University of Trieste, 34127 Trieste, Italy;
authors.forename: Paolo
authors.identifier: http://orcid.org/0000-0003-3862-4970
authors.initials: P
authors.lastname: Durigutto
authors.affiliation: Department of Life Sciences, University of Trieste, 34127 Trieste, Italy;
authors.forename: Paolo
authors.identifier: http://orcid.org/0000-0003-3079-4019
authors.initials: P
authors.lastname: Macor
authors.affiliation: Department of Life Sciences, University of Trieste, 34127 Trieste, Italy;
authors.forename: Roberta
authors.identifier: http://orcid.org/0000-0003-1737-5776
authors.initials: R
authors.lastname: Bulla
authors.affiliation: Department of Chemistry, University of Milan, 20133 Milan, Italy;
authors.forename: Alessandro
authors.identifier: http://orcid.org/0000-0002-5287-1663
authors.initials: A
authors.lastname: Palmioli
authors.affiliation: Department of Chemistry, University of Milan, 20133 Milan, Italy;
authors.forename: Anna
authors.identifier: http://orcid.org/0000-0002-1258-2007
authors.initials: A
authors.lastname: Bernardi
authors.affiliation: Dipartimento di Neuroscienze, Istituto di Ricerca e Cura a Carattere Scientifico - Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy;
authors.forename: Maria-Grazia
authors.identifier: http://orcid.org/0000-0001-6695-5297
authors.initials: MG
authors.lastname: De Simoni
authors.affiliation: MatriceLAB Innove, Hôpital Saint Louis, 75010 Paris, France;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ledee
authors.affiliation: U 976 INSERM, Hôpital Saint Louis, 75010 Paris, France; and.
authors.forename: Gerard
authors.initials: G
authors.lastname: Chaouat
authors.affiliation: Istituto di Ricerca e Cura a Carattere Scientifico - Istituto Auxologico Italiano, 20095 Milan, Italy tedesco@units.it.
authors.forename: Francesco
authors.identifier: http://orcid.org/0000-0003-2462-0493
authors.initials: F
authors.lastname: Tedesco
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D003182:Complement C5 / Q000276:immunology / Q000378:metabolism; D037582:Complement Pathway, Mannose-Binding Lectin / Q000187:drug effects; D004195:Disease Models, Animal; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000276:immunology; D011247:Pregnancy
chemical_list: D019138:Antibodies, Blocking; D003182:Complement C5; D037601:Mannose-Binding Lectin; C069858:mannose binding protein A