Crosstalk between red blood cells and the immune system and its impact on atherosclerosis.
Atherosclerosis is a chronic multifactorial disease of the arterial wall characterized by inflammation, oxidative stress, and immune system activation. Evidence exists on a pathogenic role of oxidized red blood cells (RBCs) accumulated in the lesion after intraplaque hemorrhage. This review reports current knowledge on the impact of oxidative stress in RBC modifications with the surface appearance of senescent signals characterized by reduced expression of CD47 and glycophorin A and higher externalization of phosphatidylserine. The review summarizes findings indicating that oxidized, senescent, or stored RBCs, due to surface antigen modification and release of prooxidant and proinflammatory molecules, exert an impaired modulatory activity on innate and adaptive immune cells and how this activity contributes to atherosclerotic disease. In particular RBCs from patients with atherosclerosis, unlike those from healthy subjects, fail to control lipopolysaccharide-induced DC maturation and T lymphocyte apoptosis. Stored RBCs, accompanied by shedding of extracellular vesicles, stimulate peripheral blood mononuclear cells to release proinflammatory cytokines, augment mitogen-driven T cell proliferation, and polarize macrophages toward the proinflammatory M1 activation pathway. Collectively, literature data suggest that the crosstalk between RBCs with immune cells represents a novel mechanism by which oxidative stress can contribute to atherosclerotic disease progression and may be exploited for therapeutic interventions.
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Brigitta
0000-0002-0575-4106
B
Buttari
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Elisabetta
0000-0002-7261-8884
E
Profumo
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Rachele
R
Riganò
D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051928:CD47 Antigen / Q000378:metabolism; D049109:Cell Proliferation; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006021:Glycophorins / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D051928:CD47 Antigen; C497894:CD47 protein, human; D006021:Glycophorins