Internalization of cell-derived microparticles triggers endothelial pro-inflammatory responses

Asian Pac J Allergy Immunol. 2021 Apr 18. doi: 10.12932/AP-040920-0952. Online ahead of print.

Abstract

Background: Increased numbers of circulating microparticles (MPs) have long been documented in thalassemia and are considered as a contributing factor in developing the thromboembolic events (TEEs), which are associated with endothelial dysfunction. Indeed, the cellular and molecular mechanisms by which MPs and endothelial cells interact and their consequences remain poorly investigated.

Objective: The present study aims to compare the biological effects of MPs obtained from healthy subjects and β-thalassemia/HbE patients on endothelial pro-inflammatory responses.

Methods: MPs isolated from plasma by two-step centrifugation from 10 healthy donors, 19 splenectomized and 30 non-splenectomized β-thalassemia/HbE patients were first characterized for their cellular origins, then counted and incubated with primary human umbilical vein endothelial cells (HUVECs). Internalization of MPs into HUVECs and their induction on endothelial cell activation and pro-inflammatory responses were determined.

Results: MPs either from healthy or β-thalassemia/HbE patients could become internalized into endothelial cells, but unlike MPs from healthy donors and non-splenectomized patients, MPs from splenectomized patients were the most active and induced the 2-fold up-regulation of pro-inflammatory genes, IL1B, CXCL8, and CCL2 and 4-fold increase in interleukin-1β. In addition, MPs from both healthy subjects and splenectomized patients at 106/ml failed to trigger the secretion of endothelial IL-6 and IL-8 while higher MP concentration at 5 × 10⁶/ml significantly induced this secretion.

Conclusions: Plasma MPs isolated from splenectomized β-thalassemia/HbE patients are capable of triggering pro-inflammatory responses from endothelial cells reflected at both gene and protein levels.