2026-04-14T18:31:00Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/515732025-03-07T08:38:59Zcom_10324_1181com_10324_931com_10324_894col_10324_1387

Morales, Albert Rojo Rello, Silvia Cristóbal, Helena Fiz López, Aida Arribas Rodríguez, Elisa Mari, Montserrat Tutusaus, Anna Cal Sabater, Paloma De La Nicolaes, Gerry Ortiz Pérez, José T. Bernardo Ordiz, David García de Frutos, Pablo 2022-01-19T13:36:24Z 2022-01-19T13:36:24Z 2021 Biomedicines, 2021, vol. 9, n. 4, 335 2227-9059 https://uvadoc.uva.es/handle/10324/51573 10.3390/biomedicines9040335 Producción Científica Background: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19. Ministerio de Ciencia, Innovación y Universidades (project RTI2018-095672-B-I00) Instituto de Salud Carlos III - Fondo de Investigación Sanitaria (grants PI15/00531 and PI19/01410) Fundació La Marató TV3 (grants 20153030 and 20153031) Consejo Superior de Investigaciones Científicas (project CSIC-COV19-016/202020E155) Junta de Castilla y León (project 07.04.467B04.74011.0) application/pdf eng MDPI info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ © 2021 The Authors Attribution-NonCommercial-NoDerivatives 4.0 Internacional COVID-19 (Enfermedad) Viral infections Infecciones virales Immune responses Respuestas inmunes Inmunotrombosis Vitamin K Vitamina K Growth arrest-specific factor 6 (GAS6) is increased in COVID-19 patients and predicts clinical outcome info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.mdpi.com/2227-9059/9/4/335 SI