Effect of heparin, dermatan sulfate, and related oligo-derivatives on human polymorphonuclear leukocyte functions.
The in vitro effect of unfractionated heparin and dermatan sulfate, as well as oligo-heparin and oligo-dermatan sulfate, on human PMN function was investigated. Superoxide anion generation in fMLP-stimulated PMN was dose-dependently reduced by heparin and oligo-heparin, while DS and oligo-DS lacked inhibitory activity. FMLP-stimulated PMN adhesion to endothelial cells was reduced to a similar extent by both heparin and oligo-heparin, but not by DS and oligo-DS. On the other hand, none of the compounds affected the adhesion of unstimulated PMN to either IL-1- or PMA-activated endothelial cells. Heparin and oligo-heparin also inhibited the homotypic aggregation of fMLP-stimulated PMN. As reported, coincubation of platelets with fMLP-stimulated PMN resulted in platelet activation, a process mainly mediated by the PMN-derived serine protease cathepsin G. Both heparin and DS, as well as their oligo-derivatives, reduced platelet activation induced by either fMLP-stimulated PMN or purified leukocytic cathepsin G. Finally, besides cathepsin G, also the activity of beta-glucuronidase and lysozyme released by stimulated PMN were reduced by heparin, oligo-heparin and DS. These data support the hypothesis that heparin and other GAGs may exert an antiinflammatory role.
Laboratory of Vascular Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
G
G
Bazzoni
A
A
Beltrán Nuñez
G
G
Mascellani
P
P
Bianchini
E
E
Dejana
A
A
Del Maschio
D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D003871:Dermatan Sulfate / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D009844:Oligosaccharides / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D009844:Oligosaccharides; D013481:Superoxides; D003871:Dermatan Sulfate; D006493:Heparin; D009113:Muramidase; D005966:Glucuronidase