Using four different glycosaminoglycans (un fractionated heparin, low-molecular-weight heparin, pen tosan polysulfate, lactobionic acid) and the polypeptide hirudin, we investigated the influence of these anticoag ulant substances on both polymorphonuclear neutrophils and monocytes respiratory burst in vitro. Using real-time analysis, we demonstrated that both unfractionated and low-molecular-weight heparins, as well as pentosan polysulfate, trigger the respiratory burst in neutrophils and monocytes within 3 to 5 s at clinically relevant con centrations. These effects could be antagonized by pre- incubating the anticoagulant drugs with protamine. Scan ning electron microscopy confirmed an activated neutro phil phenotype after exposure to the anticoagulant compounds. Furthermore, we demonstrated that neither increased intracellular Ca2+ levels nor tyrosine phos phorylation of proteins, both mechanisms commonly in volved in the signal transduction in neutrophils, partici pate in the glycosaminoglycan-mediated activation of the respiratory burst. Our results indicate that defined anti coagulant substances can trigger the respiratory burst in vitro, which might also have clinical implications in cer tain diseases. Key Words: Glycosaminoglycans— Hirudin—Polymorphonuclear leukocytes—Monocytes— Respiratory burst—Flow cytometry.
