Heparin potentiates in vivo neutrophil migration induced by IL-8.
Chemokine IL-8 attracts neutrophils by a haptotactic gradient, made possible by its interaction with proteoglycans of the extracellular matrix. Heparan sulfate, but not heparin, potentiates the attraction exerted in vitro by IL-8. In the present study we first confirmed this in vitro phenomenon, observing that IL-8 activity was potentiated 100% by heparan sulfate, but not by heparin. Then, we evaluated the interference of heparan sulfate or heparin on in vivo neutrophil migration induced by IL-8. The activity of rat IL-8 (3.5 microg/animal) preincubated with heparan sulfate (50 microg/animal) or heparin (77 microg/animal) was assayed on the rat dorsal air pouch. Contrary to in vitro experiments, heparin, but not heparan sulfate, potentiated the in vivo IL-8 activity two-fold. We investigated the relationship between this observation and that reported by others, that IL-8-induced migration depends on the presence of mast cells, which contain heparin-rich granules. We studied the neutrophil migration induced by IL-8 (3.5 microg/animal) into the rat peritoneal cavity depleted of mast cells. Neutrophil migration was reduced by 32% when compared to that observed in normal animals. The response of depleted rats was reconstituted by preincubation of IL-8 with heparin (77 microg/animal). These data suggest that heparin released from cytoplasmic granules may be the contribution of mast cells to IL-8-induced neutrophil migration.
Dias-Baruffi
M
M
Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, Brazil.
Pereira-da-Silva
G
G
Jamur
M C
MC
Roque-Barreira
M C
MC
D000818:Animals; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D051381:Rats
D006493:Heparin; D006497:Heparan Sulfate; D016209:Interleukin-8