title: Free hemoglobin: a dangerous signal for the immune system in patients with carotid atherosclerosis?
abstract: Atherosclerosis is a chronic inflammatory multifactorial disease in which immune responses are key pathogenetic factors. T cell-mediated immunity contributes to the initiation and progression of atherosclerotic disease, but the nature of antigens responsible for immune cell activation is still not completely elucidated. Convincing evidence supports a determinant role of autoimmune responses to self-structures in shaping the progression of the disease. Autoimmune responses may be directed against altered self-structures, such as oxidized low-density lipoproteins (LDL). Oxidative stress, increasingly reported in patients with atherosclerosis, is the major event causing protein structural modification, thus inducing the appearance of neo/cryptic epitopes on the molecule. Intraplaque hemorrhage, a common event in advanced lesions, causes the deposition of large amounts of hemoglobin (Hb). The pro-oxidative intraplaque microenvironment may induce structural changes in extra-erythrocytic free Hb, thus generating novel/cryptic autoantigenic epitopes. We demonstrated that an oxidized Hb preparation enriched in hemichromes expands IFN-gamma-secreting T lymphocytes in patients with advanced carotid atherosclerosis and enhances the phenotypical and functional maturation of human monocyte-derived dendritic cells induced by lipopolysaccharide (LPS). Overall, our findings suggest that oxidized forms of Hb could act as a dangerous signal for the immune system, thus contributing to the inflammatory process that takes place within the atherosclerotic plaque.
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy. rachele.rigano@iss.it.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Buttari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Profumo
authors.forename: Linda
authors.initials: L
authors.lastname: Petrone
authors.forename: Donatella
authors.initials: D
authors.lastname: Pietraforte
authors.forename: Alessandra
authors.initials: A
authors.lastname: Siracusano
authors.forename: Paola
authors.initials: P
authors.lastname: Margutti
authors.forename: Federica
authors.initials: F
authors.lastname: Delunardo
authors.forename: Elena
authors.initials: E
authors.lastname: Ortona
authors.forename: Maurizio
authors.initials: M
authors.lastname: Minetti
authors.forename: Bruno
authors.initials: B
authors.lastname: Salvati
authors.forename: Rachele
authors.initials: R
authors.lastname: Riganò
mesh_terms: D000220:Adaptation, Biological / Q000276:immunology; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001324:Autoantigens / Q000276:immunology; D002340:Carotid Artery Diseases / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology