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 biotinylated IFN-gamma bound equally well to purified peritoneal mast cells from both IFN-gammaR knockout and wild-type mice, indicating a non-IFN-gammaR binding site. Purified peritoneal mast cells, loaded with IFN-gamma for 30 min and washed, were able to induce NO synthesis by peritoneal macrophages. This response required cell contact and expression of IFN-gammaR on the responding macrophages, but not the mast cells. Human HMC-1 mast cells were also able to present IFN-gamma to mouse macrophages. Enzyme treatment of mouse mast cells revealed that binding of IFN-gamma was predominantly to chondroitin sulfate B (dermatan sulfate). Binding of IFN-gamma to dermatan sulfate was confirmed by inhibition ELISA. This study demonstrates for the first time that mast cells can present IFN-gamma to other cells via glycosaminoglycans. Mast cells may act as a reservoir of surface-stored functionally active cytokines.
Brooks
B
B
Department of Pharmacology, School of Biological Sciences, University of Liverpool, United Kingdom.
Briggs
D M
DM
Eastmond
N C
NC
Fernig
D G
DG
Coleman
J W
JW
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006025:Glycosaminoglycans / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D010529:Peritoneal Cavity / Q000166:cytology; D011485:Protein Binding / Q000276:immunology
D006025:Glycosaminoglycans; D009569:Nitric Oxide; D007371:Interferon-gamma