In an in vitro whole blood model of artificial surface-induced inflammation, we have studied the contribution of leukocyte populations in the synthesis of inflammatory mediators. This was done by depleting the blood of specific cell types using magnetic beads coated with monoclonal antibodies against leukocyte surface antigens. Synthesis of interleukin 8 (IL-8) was highly dependent on CD15+ cells and was reduced by 80% when these cells were removed from the blood. Correspondingly, IL-8 production showed a high correlation with the concentration of granulocytes (r = 0.77, p < 0.0001). Synthesis of monocyte chemoattractant protein 1 (MCP-1) was dependent on CD14+ cells and was reduced by 35% when these cells were removed from the blood. Correspondingly, MCP-1 production correlated with the concentration of monocytes (r = 0.39, p < 0.0001). Synthesis of leukotriene B4 (LTB4) was highly dependent on CD15+ cells and was reduced by 75% when these cells were removed from the blood. Correspondingly, LTB4 production correlated strongly with the granulocyte concentration (r = 0.54, p < 0.0001). As expected, complement activation was not affected by cell depletion and did not correlate with the concentration of any of the cell types. Thus, artificial surface-induced IL-8 and LTB4 synthesis was almost exclusively granulocyte dependent. However, MCP-1 synthesis was mainly a product of monocytes, although granulocytes and other subpopulations may partly contribute. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005.