Endothelial Glycocalyx Shedding Emerges as a Dual Marker for Treatment and Diagnosis in Anaphylaxis

Anaphylaxis is an acute life-threatening reaction. Research into the vascular endothelium and its components may improve disease management and patient outcomes. Objective: We investigated the endothelial glycocalyx (eGCX) and its role in the pathophysiology of murine anaphylaxis, aiming to identify novel diagnostic and therapeutic targets.

Active systemic anaphylaxis (ASA) was evaluated in mice. eGCX structure and N-acetylglucosamine residues in mouse aortic tissue were analyzed using transmission electron microscopy and wheat germ agglutinin staining. Endocan (ESM-1) levels in mouse aorta and plasma were determined using immunofluorescence and ELISA. Sulodexide was administered as a prophylactic treatment. Human sera from ß-lactam-induced anaphylaxis and endothelial cell (EC) secretome samples were also analyzed.

eGCX surface area and thickness were reduced in ASA mice. N-acetylglucosamine and ESM-1 levels decreased in aortic tissue but increased in plasma, indicating eGCX shedding. Consistently, ESM-1 secretion was enhanced in ECs exposed to acute anaphylactic sera. ESM-1 and hyaluronic acid levels differed significantly between patients with anaphylaxis and nonallergic controls. Sulodexide reduced reaction severity, increased survival, and prevented disruption of eGCX and release of ESM-1.

eGCX shedding, particularly of ESM-1, acts as a key mediator in murine anaphylaxis. Prophylaxis with sulodexide protects against severe reactions and improves survival. Therapies based on glycosaminoglycans and proteoglycans may mitigate the severity of anaphylaxis, and monitoring of eGCX dynamics could aid diagnosis.