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Hypothetical model for endothelial endoglin in leukocyte transmigration through the vessel endothelium. Upon inflammatory stimulation, soluble factors are released, including the chemokine CXCL12, leading to activation and endoglin-dependent extravasation of leukocytes (A). Leukocyte transmigration involves the binding of CXCL12 to its receptor CXCR4, which in turn activates the β1 integrins. Once activated, β1 integrin binds to the RGD motif of endoglin present on the endothelial cell (EC) surface, allowing the extravasation and migration of leukocytes to the inflammatory site (B). Soluble endoglin competes for the binding between leukocyte β1 integrin and endothelial membrane anchored endoglin, thus interfering with leukocyte adhesion and transmigration (C). See the article by Rossi et al on page 403.