Protease activity and the role of the endothelial glycocalyx in inflammation

A new paradigm for governance of leukocyte-endothelium (WBC–EC) adhesion during the inflammatory process is presented in which shedding of the endothelial glycocalyx exposes adhesion molecules on the EC surface, which promotes WBC–EC adhesion. It is postulated that the effector of this shedding is the activation of extracellular proteases, one of which may be a member of the matrix metalloproteinase (MMP) family of zinc dependent endopeptidases. This model for the role of the glycocalyx as a barrier to WBC–EC adhesion includes the additional participation of normally active extracellular proteolytic enzymes, that is, sheddases, which may cleave proteoglycans or activate lyases that cleave GAG chains in the glycocalyx. In support of this hypothesis, studies are examined which have established the concurrent activation of MMP proenzymes on the EC surface, shedding of the glycocalyx, and enhanced WBC–EC adhesion.