Free Hemoglobin: A Dangerous Signal for the Immune System in Patients with Carotid Atherosclerosis?

Authors: BUTTARI, BRIGITTA¹; PROFUMO, ELISABETTA¹; PETRONE, LINDA¹; PIETRAFORTE, DONATELLA²; SIRACUSANO, ALESSANDRA¹; MARGUTTI, PAOLA¹; DELUNARDO, FEDERICA¹; ORTONA, ELENA¹; MINETTI, MAURIZIO²; SALVATI, BRUNO³; RIGANÒ, RACHELE¹

Source: Annals of the New York Academy of Sciences, Volume 1107, Number 1, June 2007 , pp. 42-50(9)

Publisher: Blackwell Publishing

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By this author: BUTTARI, BRIGITTA ; PROFUMO, ELISABETTA ; PETRONE, LINDA ; PIETRAFORTE, DONATELLA ; SIRACUSANO, ALESSANDRA ; MARGUTTI, PAOLA ; DELUNARDO, FEDERICA ; ORTONA, ELENA ; MINETTI, MAURIZIO ; SALVATI, BRUNO ; RIGANÒ, RACHELE

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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-γ-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.

Keywords: free hemoglobin; hemichromes; oxidative stress; carotid atherosclerosis; autoantigens; T lymphocytes; dendritic cells

Document Type: Research article

DOI: 10.1196/annals.1381.005

Affiliations: 1: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy 2: Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy 3: Dipartimento di Scienze Chirurgiche, Università“La Sapienza,” Rome, Italy