Presentation of IFN-gamma to nitric oxide-producing cells: A novel function for mast cells

We report that mast cells can bind and present IFN-gamma in a functionally active form to macrophages. Flow-cytometric analysis revealed that biotinyl ated IFN-gamma bound equally well to purified peritoneal mast cells from bo th IFN-gamma R knockout and wild-type mice, indicating a non-IFN-gamma R bi nding site. Purified peritoneal mast cells, loaded with IFN-gamma for 30 mi n and washed, were able to induce NO synthesis by peritoneal macrophages. T his response required cell contact and expression of IFN-gamma R on the res ponding macrophages, but not the mast cells. Human HMC-1 mast cells were al so able to present IFN-gamma to mouse macrophages. Enzyme treatment of mous e mast cells revealed that binding of IFN-gamma was predominantly to chondr oitin sulfate B (dermatan sulfate). Binding of IFN-gamma to dermatan sulfat e was confirmed by inhibition ELISA. This study demonstrates for the first time that mast cells can present IFN-gamma to other cells via glycosaminogl ycans. Mast cells may act as a reservoir of surface-stored functionally act ive cytokines.