Fig. 8

Interactions of endothelial CLN-5⁺ EVs with leukocytes. EVs shed from endothelial cells could potentially transfer CLN-5 protein to leukocytes and foster TEM by several conceivable scenarios: [1] binding of shed CLN-5⁺ EVs to undefined sites on the leukocyte surface, [2] binding of nascent CLN-5⁺ EVs still associated with the endothelium to endogenous CLN-5 on the leukocyte surface, and [3] binding of shed CLN-5⁺ EVs to endogenous CLN-5 on the leukocyte surface, resulting in temporary cross-linking of leukocyte to the endothelium. Binding of CLN-5⁺ EVs to endogenous CLN-5 on the leukocyte surface could potentially amplify leukocyte:endothelial interactions by increasing avidity of CLN-5-binding partners. Not shown are possibilities EVs might inject endothelial-derived CLN-5 protein and/or mRNA into the leukocyte for surface expression. Concentrated release of EVs near the junctional region could act in a juxtacrine manner to guide leukocytes to this site for TEM