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Inhibition of Glycan Shedding from the Endothelial Glycocalyx and Adhesion of Leukocytes by Doxycycline in Post‐capillary Venules
Author(s) -
Lipowsky Herbert H,
Sah Rachna A,
Lescanic Ann
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.731.15
Subject(s) - chemistry , glycocalyx , adhesion , calcium , doxycycline , chelation , cell adhesion , deferoxamine , biophysics , vascular permeability , pharmacology , microbiology and biotechnology , immunology , biochemistry , biology , endocrinology , organic chemistry , antibiotics
Previous studies have demonstrated that shedding of glycans from the endothelial cell (EC) glycocalyx and leukocyte (WBC)‐EC adhesion in response to the chemoattractant fMLP could be attenuated by doxycycline (Doxy) through the inhibition of matrixmetalloproteases (MMPs). Given that Doxy is a strong calcium chelator, the present studies were undertaken to determine if the calcium chelator EDTA could produce a similar effect. To this end, WBC‐EC adhesion and adhesion of lectin (BS‐1) coated microspheres (0.1 um diameter) in post‐capillary venules of mesentery (rat) were studied during superfusion of the tissue with Ringers solution plus EDTA in the presence or absence of fMLP. In the absence of fMLP, with 1 mM EDTA sequestration of microspheres steadily increased with time, and with 3 mM sequestration reached levels 50–100% greater than without EDTA. In contrast, with 0.5 uM Doxy alone, microsphere adhesion remained constant under control conditions. Calcium chelation at levels (1 mM EDTA) that inhibited fMLP induced WBC adhesion to the same extent as Doxy (0.5 uM) caused a disruption of the venular permeability barrier that resulted in increased microsphere sequestration in the venular wall. Thus, the inhibition of microsphere shedding and WBC adhesion in response to fMLP by doxycycline appear to be caused by inhibition of MMPs in contrast to calcium chelation. Supported by R01 HL39286.