Suppression by intradermal administration of heparin of eosinophil accumulation but not oedema formation in inflammatory reactions in guinea-pig skin.
1. Heparin is widely used in the treatment of thrombotic disorders and as an aid in surgery. Anti-inflammatory effects of heparin have also been described. In this study, we have investigated the effects of locally-injected heparin on the oedema formation and eosinophil accumulation induced by various inflammatory stimuli in guinea-pig skin. 2. Heparin dose-dependently suppressed the accumulation of 111In-labelled eosinophils induced by i.d. injection of zymosan-activated plasma (ZAP). The 111In-eosinophil accumulation induced by other inflammatory stimuli (compound 48/80, platelet activating factor, interleukin-8 and in a passive cutaneous anaphylaxis reaction) was also suppressed by locally-injected heparin. 3. Oedema formation in response to these same stimuli was not altered by the local injection of heparin. 4. Fucoidin, a negatively-charged sulphated algal polymer, had no effect on the 111In-eosinophil accumulation or oedema formation induced by ZAP. Nevertheless, fucoidin significantly suppressed the oedema formation induced by i.d. injection of cationic protein-containing extracts of Schistosoma mansoni larvae. Heparin also inhibited oedema induced by the extracts, suggesting that both fucoidin and heparin were effectively neutralizing the cationic protein of the extracts to inhibit their oedema-inducing activity. 5. Thus, heparin significantly inhibited the accumulation of 111In-eosinophils, but not oedema formation, induced by various inflammatory stimuli. This, taken together with the lack of effect of fucoidin, suggests that heparin interferes with the process of eosinophil trafficking by a mechanism that does not depend on neutralisation of the charge of the stimulatory molecules.
Teixeira
M M
MM
Department of Applied Pharmacology, National Heart and Lung Institute, London.
Hellewell
P G
PG
D000279:Administration, Cutaneous; D000818:Animals; D004487:Edema / Q000517:prevention & control*; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control; D011134:Polysaccharides / Q000494:pharmacology
D011134:Polysaccharides; D006493:Heparin; C007789:fucoidan