title: Angiotensin II mobilizes spleen monocytes to promote the development of abdominal aortic aneurysm in Apoe-/- mice.
abstract: OBJECTIVE
  Abdominal aortic aneurysm (AAA) is widespread among elderly people and results in progressive expansion and rupture of the aorta with high mortality. Macrophages, which are the main population observed within the site of aneurysm, are thought to derive from circulating monocytes although no direct evidence has been provided to date. In this study, we were particularly interested in understanding the trafficking behavior of monocyte subsets in AAA and their role in disease pathogenesis.
  
  
  RESULTS
  Using bone marrow transplantation in Apoe(-/-) mice, we showed that circulating monocytes give rise to abdominal aortic macrophages in hypercholesterolemic mice submitted to angiotensin II (AngII). Detailed monitoring of monocyte compartmentalization revealed that lymphocyte antigen 6C(high) and lymphocyte antigen 6C(low) monocytes transiently increase in blood early after AngII infusion and differentially infiltrate the abdominal aorta. The splenic reservoir accounted for the mobilization of the 2 monocyte subsets after 3 days of AngII infusion. Spleen removal or lymphocyte deficiency in Apoe(-/-) Rag2(-/-) mice similarly impaired early monocyte increase in blood in response to AngII and protected against AAA development, independently of blood pressure. Reconstitution of Apoe(-/-) Rag2(-/-) mice with total splenocytes but not with B-cell-depleted splenocytes restored monocyte mobilization in response to AngII and enhanced susceptibility to AAA.
  
  
  CONCLUSIONS
  Taken together, the data show that lymphocyte antigen 6C(high) and lymphocyte antigen 6C(low) monocytes are mobilized from the spleen in response to AngII. Intriguingly, the process is dependent on the presence of B cells and significantly contributes to the development of AAA and the occurrence of aortic rupture.
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.).
authors.forename: Safa
authors.initials: S
authors.lastname: Mellak
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.).
authors.forename: Hafid
authors.initials: H
authors.lastname: Ait-Oufella
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.).
authors.forename: Bruno
authors.initials: B
authors.lastname: Esposito
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.).
authors.forename: Xavier
authors.initials: X
authors.lastname: Loyer
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.).
authors.forename: Maxime
authors.initials: M
authors.lastname: Poirier
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.).
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.).
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.).
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.affiliation: From the INSERM Unit UMR-S 970, Paris Cardiovascular Research Center (PARCC), Université Paris Descartes, Sorbonne Paris Cité, Paris, France (S.M., H.A.-O., B.E., X.L., M.P., A.T., Z.M., S.P.); Réanimation Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre-et-Marie Curie, Université Pierre-et-Marie Curie, Paris, France (H.A.-O.); Department of Immunology, Duke University Medical Center, Durham, NC (T.F.T.); and Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.). stephane.potteaux@inserm.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Potteaux
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism*; D013156:Splenectomy; D013997:Time Factors
chemical_list: D000950:Antigens, Ly; D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; C526827:Ly6 protein, mouse; C499308:Rag2 protein, mouse; D000804:Angiotensin II
keywords: B-lymphocytes; aneurysm; metabolism; monocytes; splenectomy