S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14

Changes in cytosolic calcium concentrations regulate a wide variety of cell ular processes, and calcium-binding proteins are the key molecules in signa l transduction, differentiation, and cell cycle control. S100A12, a recentl y described member of the S100 protein family, has been shown to be coexpre ssed in granulocytes and monocytes together with two other S100 proteins, M RP8 (S100A8) and MRP14 (S100A9), and a functional relationship between thes e three S100 proteins has been suggested. Using Western blotting, calcium o verlays, intracellular flow cytometry, and cytospin preparations, we demons trate that S100A12 expression in leukocytes is specifically restricted to g ranulocytes and that S100A12 represents one of the major calcium-binding pr oteins in these cells. S100A12, MRPS, and MRP14 translocate simultaneously from the cytosol to cytoskeletal and membrane structures in a calcium-depen dent manner. However, no evidence for direct protein-protein interactions o f S100A12 with either MRPS or MRP14 or the heterodimer was found by chemica l cross-linking, density gradient centrifugation, mass spectrometric measur ements, or yeast two hybrid detection. Thus, S100A12 acts individually duri ng calcium-dependent signaling, independent of MRP8, MRP14, and the heterod imer MRP8/ MRP14. This granulocyte-specific signal transduction pathway may offer attractive targets for therapeutic intervention with exaggerated gra nulocyte activity in pathological states.