Shear‐Dependent Adhesion of Leukocytes and Lectins to the Endothelium and Concurrent Changes in Thickness of the Glycocalyx of Post‐Capillary Venules in the Low‐Flow State. (15th February 2013)

• Record Type: Journal Article
• Authors: Lipowsky, Herbert H.; Lescanic, Anne
• Is Part Of: Microcirculation. Volume 20:Number 2(2013:Feb.)
• Page Start: 149
• Page End: 157
• Publication Date: 2013-02-15
• Subjects: Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12013
• Languages: English
• ISSNs: 1073-9688

Abstract

<abstract abstract-type="main" xml:lang="en" id="micc12013-abs-0001"> <title>Abstract</title> <sec id="micc12013-sec-0001" sec-type="section"> <title>Objective</title> <p>To elucidate shear‐dependent effects of deformation of the endothelial glycocalyx on adhesion of circulating ligands in post‐capillary venules, and delineate effect of MMPs.</p> </sec> <sec id="micc12013-sec-0002" sec-type="section"> <title>Methods</title> <p>Adhesion of WBCs and lectin‐coated FLMs (0.1 μm diameter) to EC of post‐capillary venules in mesentery was examined during acute reductions in shear rates (<inline-graphic mimetype="image" xlink:href="ark:/27927/pgg1s08h221" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="urn:x-wiley:10739688:media:micc12013:micc12013-math-0001" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover><mml:mrow><mml:mi mathvariant="italic">γ</mml:mi></mml:mrow><mml:mo>·</mml:mo></mml:mover><mml:mo>, </mml:mo></mml:mrow></mml:math> hemorrhagic hypotension). Adhesion was examined with or without superfusion with 0.5 μ<sc>m</sc> doxycycline to inhibit MMPs. Thickness of the glycocalyx was measured by exclusion of fluorescent 70 kDa dextran from the EC surface.</p> </sec> <sec id="micc12013-sec-0003" sec-type="section"> <title>Results</title> <p>During superfusion with Ringers, rapid reductions in <inline-graphic mimetype="image" xlink:href="ark:/27927/pgg1s08h21g" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="urn:x-wiley:10739688:media:micc12013:micc12013-math-0002" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover><mml:mrow><mml:mi mathvariant="italic">γ</mml:mi></mml:mrow><mml:mo>·</mml:mo></mml:mover></mml:mrow></mml:math> resulted in a significant rise in WBC adhesion and a twofold rise in microsphere adhesion. With addition of doxycycline WBC and FLM adhesion increased twofold under high‐ and low‐flow conditions. FLM adhesion was invariant with <inline-graphic mimetype="image" xlink:href="ark:/27927/pgg1s08h1x9" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="urn:x-wiley:10739688:media:micc12013:micc12013-math-0003" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover><mml:mrow><mml:mi mathvariant="italic">γ</mml:mi></mml:mrow><mml:mo>·</mml:mo></mml:mover></mml:mrow></mml:math> throughout the network in the normal (high)‐flow state. With reductions in <inline-graphic mimetype="image" xlink:href="ark:/27927/pgg1s08h19c" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="urn:x-wiley:10739688:media:micc12013:micc12013-math-0004" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover><mml:mrow><mml:mi mathvariant="italic">γ</mml:mi></mml:mrow><mml:mo>·</mml:mo></mml:mover><mml:mo>, </mml:mo></mml:mrow></mml:math> thickness of the glycocalyx increased significantly, with or without doxycycline.</p> </sec> <sec id="micc12013-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The concurrent increase in WBC and FLM adhesion with increased thickness of the glycocalyx during reductions in shear suggests that glycocalyx core proteins recoil from their deformed steady‐state configuration, which increases exposure of binding sites for circulating ligands.</p> </sec> </abstract>