The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases

Herbert H. Lipowsky

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

The endothelial cell (EC) surface is coated with a layer of polysaccharides linked to membrane-bound and trans-membrane proteoglycans that comprise the glycocalyx, which is augmented by adsorbed proteins derived from the blood stream. This surface layer has been shown to affect hemodynamics in small blood vessels of the microcirculation, the resistance to flow, and leukocyte (WBC) to EC adhesion. Parallel studies of WBC-EC adhesion in response to chemo-attractants and cytokines, and shedding of constituents of the glycocalyx, have suggested a role for activation of extracellular proteases in mediating the dynamics of WBC adhesion in response to inflammatory and ischemic stimuli. Likely candidates among the many proteases present are the matrix metalloproteases (MMPs). Inhibition of MMP activation with sub-antimicrobial doses of doxycycline, or zinc chela-tors, has also inhibited WBC adhesion and shedding of glycans from the EC surface in response to the chemoattrac-tant fMLP. Taken together, these studies suggest that shedding of the EC glycocalyx exposes adhesion receptors and thus enhances WBC-EC adhesion. Future therapeutic strategies for treating pathologies such as the low flow state and inflammation may benefit by further exploration of the mechanics of the glycocalyx in light of protease activation and shear-dependent effects.

Original languageEnglish (US)
Pages (from-to)840-848
Number of pages9
JournalAnnals of Biomedical Engineering
Volume40
Issue number4
DOIs
StatePublished - Apr 1 2012

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering

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