Katacalcin is a potent plasma calcium lowering peptide. Katacalcin belongs to the calcitonin family, that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of these ions in the bones. Katacalcin (KC) belongs to a small family of polypeptides that are encoded by the calc-1 gene and also include calcitonin (CT) and procalcitonin NH2-terminal cleavage peptide (N-ProCT). Katacalcin pretreatment leads to a concentration-dependent decrease at concentrations between 1 amol/liter and 10 fmol/liter and is a more potent inhibitor of fMLP-induced chemotaxis than CT or procalcitonin (PCT). Katacalcin deactivates CD14 + peripheral blood mononuclear cell (PBMC) chemotaxis not only toward N-formyl-Met-Leu-Phe (fMLP) but also toward other attractants of the chemokine family (heterologous deactivation) as well as toward PCT and CT. Pretreatment of CD14 + PBMCs with Katacalcin also deactivates subsequent chemotaxis toward Katacalcin itself. Katacalcin elicites concentration-dependent migration of CD14 + PBMC at concentrations from the atomolar to the micromolar range and deactivates attractant-induced chemotaxis. Katacalcin regulates human CD14 + PBMC migration via signaling events involving protein kinase A-dependent cAMP pathways.