In Mac-1-mediated signaling, Src family kinases activate non-receptor tyrosine kinases Syk and Pyk2 by tyrosine phosphorylation.52–54 From top left to bottom right: TNF-induced release of secondary granules from adherent human PMNs is dependent on Mac-1-integrin-triggered oscillations of cytosolic free Ca2+.34 Src family kinases are involved in the spontaneous release of secondary granules from human PMNs adherent on TCPS.37 Syk is involved in the release of secondary granules from murine PMNs adherent on fibrinogen-coated surfaces in response to TNF stimulation.35 Pyk2 is involved in the TNF-induced release of secondary and tertiary granules from murine PMNs adherent on poly-RGD surfaces.36 Bold boxes: In this study, we found that Src family kinases are involved in the spontaneous release of primary granules from PMNs cultured on PEG hydrogels, TCPS and GP hydrogels and that Src family kinases are also involved in the spontaneous release of tertiary granules from PMNs cultured on PEG hydrogels, PDMS, TCPS, and GP hydrogels.