An endothelial proinflammatory phenotype precedes the development of the engraftment syndrome after autologous Hct.

Abstract

Engraftment syndrome (ES) is a common complication after autologous hematopoietic cell transplantation (auto-HCT) whose pathophysiological substrate remains unclear. We investigated whether endothelial damage could contribute to ES. Circulating ECs-damage biomarkers were measured in plasma from patients with (ES; n = 14) or without ES (non-ES; n = 20), collected at different time points: before HCT, 5 (S5) and 10 days (S10) after HCT, and at either the ES onset (SON) or the discharge day (SDIS). Also, cultured endothelial cells (ECs) were exposed to serum samples, obtained at the same points, to evaluate changes in ECs-activation (ICAM-1, VE-Cadherin) biomarkers, the reactivity of ECs towards leukocytes, and activation of intracellular signaling proteins related to inflammation (p38MAPK) and proliferation (Erk1/2). Results showed that circulating VWF, sTNFR1 and sVCAM-1 levels were higher in ES patients at all the points assessed, especially at SON. In vitro results showed an increased ICAM-1 expression on ECs exposed to ES samples vs. non-ES samples, especially to S5, with elevated leukocyte adhesion. Also, a lower VE-Cadherin expression and an increased phosphorylation of p38MAPK and Erk1/2 proteins were observed in ECs exposed to ES vs. non-ES samples. Our results indicate that endothelial activation precedes ES development and could be one of its pathophysiological substrates.

• Authors: Ana Belén Moreno-Castaño, Marta Palomo, Sergi Torramadé-Moix, Julia Martinez-Sanchez, Alex Ramos, Patricia Molina, Marc Pino, Pilar Gómez-Ramírez, Laura Bonastre, Maria Teresa Solano, Ginés Escolar, Montserrat Rovira, Luis Gerardo Rodríguez-Lobato, Gonzalo Gutiérrez-García, Enric Carreras, Francesc Fernández-Avilés, Maribel Diaz-Ricart
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 57 Issue 5 Pg. 721-728 (05 2022) ISSN: 1476-5365 [Electronic] England
• PMID: 35184147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Biomarkers
• Intercellular Adhesion Molecule-1

Topics

• Biomarkers (metabolism)
• Endothelial Cells (metabolism)
• Hematologic Diseases
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Immune System Diseases
• Intercellular Adhesion Molecule-1
• Phenotype