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Presentation of IFN- to Nitric Oxide-Producing Cells: A Novel Function for Mast Cells¹

Bernadette Brooks^*, David M. Briggs^*, Nigel C. Eastmond^*, David G. Fernig and John W. Coleman^2,*

^* Department of Pharmacology and Therapeutics, and School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom

We report that mast cells can bind and present IFN- in a functionally active form to macrophages. Flow-cytometric analysis revealed that biotinylated IFN- bound equally well to purified peritoneal mast cells from both IFN-R knockout and wild-type mice, indicating a non-IFN-R binding site. Purified peritoneal mast cells, loaded with IFN- for 30 min and washed, were able to induce NO synthesis by peritoneal macrophages. This response required cell contact and expression of IFN-R on the responding macrophages, but not the mast cells. Human HMC-1 mast cells were also able to present IFN- to mouse macrophages. Enzyme treatment of mouse mast cells revealed that binding of IFN- was predominantly to chondroitin sulfate B (dermatan sulfate). Binding of IFN- to dermatan sulfate was confirmed by inhibition ELISA. This study demonstrates for the first time that mast cells can present IFN- to other cells via glycosaminoglycans. Mast cells may act as a reservoir of surface-stored functionally active cytokines.

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