OBJECTIVE: Levels of S100A8/A9, a proinflammatory and prothrombotic protein complex, are increased in several diseases, and high levels predispose to cardiovascular disease (CVD). Recently, platelet S100A8/A9 synthesis was described in mice and humans in relation to CVD. The aim of this study was to investigate the role of platelet S100A8/A9 in systemic lupus erythematosus (SLE), a disease with markedly increased cardiovascular morbidity, as well as the exact platelet distribution of the S100A8/A9 proteins. METHODS: The occurrence and distribution of platelet S100A8/A9 protein were detected by enzyme-linked immunosorbent assay, electron microscopy, Western blotting, and flow cytometry in healthy controls (n = 79) and in 2 individual cohorts of SLE patients (n = 148 and n = 318, respectively) and related to cardiovascular morbidity. RESULTS: We observed that human platelets expressed S100A8/A9 proteins, and that these were localized in close proximity to intracellular membranes and granules as well as on the cell surface upon activation with physiologic and pathophysiologic stimuli. Interestingly, S100A8/A9 was enriched at sites of membrane interactions, indicating a role of S100A8/A9 in cell-cell communication. S100A8/A9 levels were highly regulated by interferon-α, both in vivo and in vitro. Patients with SLE had increased platelet S100A8/A9 content compared with healthy individuals. Increased levels of platelet S100A8/A9 were associated with CVD, particularly myocardial infarction (odds ratio 4.8, 95% confidence interval 1.5-14.9, P = 0.032 [adjusted for age, sex, and smoking]). CONCLUSION: Platelets contain S100A8/A9 in membrane-enclosed vesicles, enabling rapid cell surface deposition upon activation. Furthermore, platelet S100A8/A9 protein levels were increased in SLE patients, particularly in those with CVD, and may be a future therapeutic target.
OBJECTIVE: Levels of S100A8/A9, a proinflammatory and prothrombotic protein complex, are increased in several diseases, and high levels predispose to cardiovascular disease (CVD). Recently, platelet S100A8/A9 synthesis was described in mice and humans in relation to CVD. The aim of this study was to investigate the role of platelet S100A8/A9 in systemic lupus erythematosus (SLE), a disease with markedly increased cardiovascular morbidity, as well as the exact platelet distribution of the S100A8/A9 proteins. METHODS: The occurrence and distribution of platelet S100A8/A9 protein were detected by enzyme-linked immunosorbent assay, electron microscopy, Western blotting, and flow cytometry in healthy controls (n = 79) and in 2 individual cohorts of SLEpatients (n = 148 and n = 318, respectively) and related to cardiovascular morbidity. RESULTS: We observed that human platelets expressed S100A8/A9 proteins, and that these were localized in close proximity to intracellular membranes and granules as well as on the cell surface upon activation with physiologic and pathophysiologic stimuli. Interestingly, S100A8/A9 was enriched at sites of membrane interactions, indicating a role of S100A8/A9 in cell-cell communication. S100A8/A9 levels were highly regulated by interferon-α, both in vivo and in vitro. Patients with SLE had increased platelet S100A8/A9 content compared with healthy individuals. Increased levels of platelet S100A8/A9 were associated with CVD, particularly myocardial infarction (odds ratio 4.8, 95% confidence interval 1.5-14.9, P = 0.032 [adjusted for age, sex, and smoking]). CONCLUSION: Platelets contain S100A8/A9 in membrane-enclosed vesicles, enabling rapid cell surface deposition upon activation. Furthermore, platelet S100A8/A9 protein levels were increased in SLEpatients, particularly in those with CVD, and may be a future therapeutic target.
Authors: Barbora Šumová; Lucie Andrés Cerezo; Lenka Szczuková; Lucie Nekvindová; Michal Uher; Hana Hulejová; Radka Moravcová; Mariam Grigorian; Karel Pavelka; Jiří Vencovský; Ladislav Šenolt; Jakub Závada Journal: Rheumatol Int Date: 2018-11-03 Impact factor: 2.631
Authors: Victoria Carter; John LaCava; Martin S Taylor; Shu Ying Liang; Cecilia Mustelin; Kennedy C Ukadike; Anders Bengtsson; Christian Lood; Tomas Mustelin Journal: Arthritis Rheumatol Date: 2020-01 Impact factor: 10.995
Authors: Mary Bach; Jeonghun Moon; Richard Moore; Tiffany Pan; J Lee Nelson; Christian Lood Journal: Arthritis Rheumatol Date: 2019-12-03 Impact factor: 10.995
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Authors: Petrus Linge; Paul R Fortin; Christian Lood; Anders A Bengtsson; Eric Boilard Journal: Nat Rev Rheumatol Date: 2018-03-21 Impact factor: 20.543
Authors: Stanley Moore; Hsin-Hsuan Juo; Christoffer T Nielsen; Helena Tyden; Anders A Bengtsson; Christian Lood Journal: J Rheumatol Date: 2019-12-15 Impact factor: 4.666
Authors: Imene Melki; Isabelle Allaeys; Nicolas Tessandier; Benoit Mailhot; Nathalie Cloutier; Robert A Campbell; Jesse W Rowley; David Salem; Anne Zufferey; Audrée Laroche; Tania Lévesque; Natalie Patey; Joyce Rauch; Christian Lood; Arnaud Droit; Steven E McKenzie; Kellie R Machlus; Matthew T Rondina; Steve Lacroix; Paul R Fortin; Eric Boilard Journal: Blood Date: 2020-12-17 Impact factor: 22.113