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Heparin potentiates in vivo neutrophil migration induced by IL-8
Authors:Marcelo Dias-Baruffi  Gabriela Pereira-da-Silva  Maria Celia Jamur  Maria Cristina Roque-Barreira
Institution:(1) Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, University of Sao Paulo, 14049-903 Ribeirao Preto, SP, Brazil;(2) Department of Parasitology, Microbiology and Immunology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, 14049-900 Ribeirao Preto, SP, Brazil;(3) Department of Cell Biology, Federal University of Parana, 81331-970 Curitiba, PR, Brazil
Abstract: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 mgrg/animal) preincubated with heparan sulfate (50 mgrg/animal) or heparin (77 mgrg/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 mgrg/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 mgrg/animal). These data suggest that heparin released from cytoplasmic granules may be the contribution of mast cells to IL-8-induced neutrophil migration.
Keywords:IL-8  heparin  heparan sulfate  mast cell  neutrophil migration
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