Dextran sulfate prevents LTB4-induced permeability increase, but not neutrophil emigration, in the hamster cheek pouch

Abstract

Leukotriene B4 (LTB4) is known to induce neutrophil-dependent macromolecular leakage in the hamster cheek pouch. LTB4 was superfused over cheek pouches dissected for intravital microscopy; and leukocyte rolling and firm adhesion in venules, neutrophil emigration, and macromolecular permeability as leakage of fluorescent dextran was quantified. Dextran sulfate (MW 500,000; 17.5 mg/kg iv bolus), but not uncharged dextran, reduced the LTB4-induced venular leakage of macromolecules by 85%. Histamine-induced leakage, which is neutrophil independent, was left unaffected. Dextran sulfate had no effect on leukocyte adhesion in postcapillary venules induced by LTB4, nor on their subsequent emigration to the surrounding tissue. Dextran sulfate significantly inhibited leukocyte rolling during nonstimulated conditions along the walls of collecting venules, but not postcapillary venules. Consequently, neutrophil-induced macromolecular leakage and neutrophil emigration appear to be independent, separable events. As an explanation of the present results it is proposed that the dextran sulfate complexes neutrophil granule cationic proteins, thus preventing neutrophil-mediated permeability increase.