Inhibition of ICAM-mediated monocyte adhesion with a bioresponsive dextran-based conjugate

The polysaccharide dextran, prepared as a colloid suspension in physiological saline, is routinely used as a plasma extender or substitute for emergency treatment of massive blood and fluid loss in settings where blood and blood products are not readily available. The objective of this study is to develop a dextran-peptide conjugate that selectively self-assembles onto injured tissue surfaces to form a protective colloid barrier against trauma-induced systemic inflammatory cell damage to healthy tissues. Endothelial cells were treated in vitro with a CD11b/CD18 antagonist conjugated to dextran. This agonist peptide conjugated to dextran decreased monocyte adhesion to TNF /spl alpha/-activated endothelium more effectively than peptide alone. The scrambled version of the same peptide, conjugated and not, did not block monocyte adhesion in similarly activated endothelium. These studies indicate that an CD11b/CD18 antagonist dextran conjugate that is delivered introvascularly may limit organ damage following intestinal ischemia and reperfusion injury.