The Endothelial Glycocalyx as a Barrier to Leukocyte Adhesion and Its Mediation by Extracellular Proteases
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...
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| Veröffentlicht in: | Annals of biomedical engineering 2012-04, Vol.40 (4), p.840-848 |
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| description | 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 chemoattractants 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 chelators, has also inhibited WBC adhesion and shedding of glycans from the EC surface in response to the chemoattractant 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. |
| doi_str_mv | 10.1007/s10439-011-0427-x |
| format | Article |
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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.</description><identifier>ISSN: 0090-6964</identifier><identifier>EISSN: 1573-9686</identifier><identifier>EISSN: 1521-6047</identifier><identifier>DOI: 10.1007/s10439-011-0427-x</identifier><identifier>PMID: 21984514</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Activation ; Adhesion ; Animals ; Biochemistry ; Biological and Medical Physics ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Biophysics ; Cell Adhesion - physiology ; Cell Adhesion Molecules - metabolism ; Cell Movement - drug effects ; Cell Movement - physiology ; Chemotactic Factors - metabolism ; Classical Mechanics ; Endothelial Cells - cytology ; Endothelial Cells - metabolism ; Enzyme Activation - drug effects ; Enzyme Activation - physiology ; Glycan ; Glycocalyx - metabolism ; Humans ; Leukocytes ; Leukocytes - enzymology ; Matrix Metalloproteinases - metabolism ; N-Formylmethionine Leucyl-Phenylalanine - pharmacology ; Polysaccharides - metabolism ; Protease ; Proteoglycans ; Saccharides ; Shedding ; Zinc</subject><ispartof>Annals of biomedical engineering, 2012-04, Vol.40 (4), p.840-848</ispartof><rights>Biomedical Engineering Society 2011</rights><rights>Biomedical Engineering Society 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c600t-a75cf1d536ac1c232be4e6e91cc7c76f1af89d9f574483bcac826bbf8d74234f3</citedby><cites>FETCH-LOGICAL-c600t-a75cf1d536ac1c232be4e6e91cc7c76f1af89d9f574483bcac826bbf8d74234f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10439-011-0427-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10439-011-0427-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21984514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lipowsky, Herbert H.</creatorcontrib><title>The Endothelial Glycocalyx as a Barrier to Leukocyte Adhesion and Its Mediation by Extracellular Proteases</title><title>Annals of biomedical engineering</title><addtitle>Ann Biomed Eng</addtitle><addtitle>Ann Biomed Eng</addtitle><description>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. 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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.</description><subject>Activation</subject><subject>Adhesion</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and Medical Physics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Biophysics</subject><subject>Cell Adhesion - physiology</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Movement - drug effects</subject><subject>Cell Movement - physiology</subject><subject>Chemotactic Factors - metabolism</subject><subject>Classical Mechanics</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - metabolism</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Activation - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of biomedical engineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lipowsky, Herbert H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Endothelial Glycocalyx as a Barrier to Leukocyte Adhesion and Its Mediation by Extracellular Proteases</atitle><jtitle>Annals of biomedical engineering</jtitle><stitle>Ann Biomed Eng</stitle><addtitle>Ann Biomed Eng</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>40</volume><issue>4</issue><spage>840</spage><epage>848</epage><pages>840-848</pages><issn>0090-6964</issn><eissn>1573-9686</eissn><eissn>1521-6047</eissn><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 chemoattractants 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 chelators, has also inhibited WBC adhesion and shedding of glycans from the EC surface in response to the chemoattractant 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.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>21984514</pmid><doi>10.1007/s10439-011-0427-x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Annals of biomedical engineering, 2012-04, Vol.40 (4), p.840-848 |
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| source | MEDLINE; SpringerNature Journals |
| subjects | Activation Adhesion Animals Biochemistry Biological and Medical Physics Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Biophysics Cell Adhesion - physiology Cell Adhesion Molecules - metabolism Cell Movement - drug effects Cell Movement - physiology Chemotactic Factors - metabolism Classical Mechanics Endothelial Cells - cytology Endothelial Cells - metabolism Enzyme Activation - drug effects Enzyme Activation - physiology Glycan Glycocalyx - metabolism Humans Leukocytes Leukocytes - enzymology Matrix Metalloproteinases - metabolism N-Formylmethionine Leucyl-Phenylalanine - pharmacology Polysaccharides - metabolism Protease Proteoglycans Saccharides Shedding Zinc |
| title | The Endothelial Glycocalyx as a Barrier to Leukocyte Adhesion and Its Mediation by Extracellular Proteases |
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