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Glycocalyx modifications induced by ischemia reperfusion (I/R) are in part mediated by membrane CD44 in striated muscle microvessels.
Author(s) -
RubioGayosso Ivan,
Day Kathleen H,
Ramos Susan,
Duling Brian R
Publication year - 2006
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.20.5.a1166
Subject(s) - glycocalyx , internalization , intravital microscopy , cremaster muscle , microbiology and biotechnology , chemistry , cd44 , microcirculation , intracellular , biology , cell , biochemistry , medicine
Hyaluronan (HA) is an important component of the luminal endothelial glycocalyx (Gcx) and plays a critical role in maintaining the exclusion of anionic macromolecules such as dextran FITC 70 kDa (Dex 70‐FITC). CD44 and HA are present in almost every cell, and therefore they are involved in many intracellular and extracellular functions. CD44 is involved in the anchoring, internalization and degradation of HA. We previously showed that HA is degraded by the I/R injury and the integrity of the Gcx can be restored by infusion of exogenous HA. We hypothesize that in CD44 −/− mice the I/R induced Gcx modification will be altered. Intravital microscopy of mouse cremaster was used to evaluate the effects induced by I/R on the Gcx of capillaries and postcapillary venules. We defined the Gcx by the exclusion of the red blood cells (RBC) and Dex 70‐FITC from the vessels wall. B6129SF1/J and C57bl/6 mice were used as controls. Cremasters from CD44 −/− mice have a large number of vessels and in the capillaries the exclusions of RBC and Dex 70‐FITC have similar dimensions as in the capillaries of control mice. However, in the cremasteric postcapillary venules of CD44 −/− mice the Gcx exclusion of RBC and Dex 70‐FITC is significantly larger. I/R induces a reduction of the Gcx exclusion of Dex 70‐FITC by 50% in capillaries and postcapillary venules of control mice. In CD44 −/− mice, I/R induces a smaller reduction of the Dex 70‐FITC exclusion zone; 16% in capillaries and 37.5 % in postcapillary venules. Infusion of exogenous HA was able to restore the reduced Gcx in CD44 −/− mice. Our results suggest that CD44 is involved in the signaling pathway induced subsequent to I/R in the microvascular Gcx. Our data also suggest that other HA binding could be anchoring the HA in the microvessels in the CD44−/−. This research was supported by NIH Grant #HL72864.