Signals of cell death and tissue turnover during physiological pregnancy, pre-eclampsia, and autoimmunity.
Apoptosis normally occurs in the human placenta. As a consequence, cell blebs, post-apoptotic debris (also referred to as syncytial knots) and membrane microparticles are released into the blood of pregnant women. These events become prominent during the best-characterized pregnancy complication, pre-eclampsia. An excessive or deregulated cell death, which results in the generation of an overwhelming burden of apoptotic material, alarms the immune system. This plays a role in the pathogenesis of systemic connective tissue diseases and possibly of small vessels vasculitis. Infiltration of leukocytes and activation of endothelial cells and platelets are hallmarks of normal pregnancy, indicating that physiologic pregnancy is a condition characterized by an activation of the innate immune system. Conversely, a failure in the physiologic termination of inflammatory events is probably a requirement for pre-eclampsia to develop. Here, we discuss recent findings suggesting a link between deregulated disposal of placental debris, the generation of endogenous pro-inflammatory signals (alarmins) and the widespread vascular inflammation that characterizes on one hand pre-eclampsia and on the other systemic autoimmune diseases.
Rovere-Querini
Patrizia
P
Clinical Immunology Unit, H San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milano, Italy. patrizia.rovere@hsr.it
Castiglioni
Maria Teresa
MT
Sabbadini
Maria Grazia
MG
Manfredi
Angelo A
AA
D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D001792:Blood Platelets / Q000276:immunology / Q000473:pathology; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D010920:Placenta / Q000276:immunology* / Q000473:pathology; D011225:Pre-Eclampsia / Q000097:blood / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction / Q000276:immunology*; D014657:Vasculitis / Q000097:blood / Q000276:immunology / Q000473:pathology