RAPID SECRETION OF PRESTORED INTERLEUKIN-8 FROM WEIBEL-PALADE BODIES OF MICROVASCULAR ENDOTHELIAL-CELLS

Interleukin (IL)-8, a C-X-C chemokine, activates integrin-mediated adh esion of neutrophils. Presentation of IL-8 on the endothelial cell sur face may promote leukocyte extravasation. We found that cultured human microvascular endothelial cells from the intestine (HIMEC) and from n asal polyps (PMEC), but not human umbilical vein endothelial cells (HU VEC), contained IL-8 in intracellular granules that coexpressed von Wi llebrand factor (vWf). This observation was corroborated by the immuno histochemical observation of double-positive granules (IL-8(+)vWf(+)) in vessels of small and large intestine, nasal mucosa, and skin, where as umbilical cords revealed no endothelial IL-8. After treatment of HI MEC or PMEC with histamine or thrombin, a dramatic increase in superna tant IL-8 concentration was observed within 3 min, whereas no increase in IL-8 was detected in supernatants of identically treated HUVEC cul tures. Histamine or thrombin treatment also caused IL-8-containing gra nules to rapidly disappear from HIMEC. In HUVEC, IL-8-containing granu les were inducible by treatment with recombinant human IL-1 beta for 2 4 h; additional histamine treatment doubled IL-8 secretion from HUVEC in the same rapid manner observed for mucosal EC. These data suggested that IL-8 prestored in microvascular endothelial cells may provide a rapid pathway for specific activation of neutrophil adhesion at sites of acute inflammation.