The major calcium-binding proteins expressed in phagocytes are myeloid-related protein 8 (MRP8 [S100A8]) and MRP14 (S100A9). Phagocytes have the ability to migrate rapidly along the activated endothelium to sites of inflammation. MRP14 knockout (ko) cells spontaneously adhered to a greater extend and transmigrated more in number than wildtype cells. Wildtype cells showed a higher basal surface expression of CD49d when compared to the ko. However, after 1 hour of adhesion, the CD49d expression level was downregulated in the wildtype and upregulated in the ko cells. Accordingly, adhesion patterns of wildtype and ko cells reversed in the presence of primary ligands of CD49d. Upon blocking CD49d expression, the adhesion and transmigration ability of the ko cells decreased. Src and Syk kinases were found to be dysregulated in ko cells compared to wildtype cells. Our data precisely indicates that MRP8/14 definitely modulates the function of migrating phagocytes and successfully guides their path along the activated endothelium.