Schematic summary of the integrin/MMP complex in PMNs. The α_Mβ₂/MMP-9 complex is formed in PMN intracellular granules and can be rapidly mobilized to the cell surface after exposure to degranulation stimuli, such as TNF-β, LPS, and fMLP. PMN degranulation can also be achieved when cells are in contact with ECM proteins. Upon PMN activation, cell-surface receptors are routinely shed from PMNs. Loss of these receptors is mainly due to PMN-derived MMP activity, a process that facilitates PMN rolling and migration via degradation of the vascular basement membrane during PMN extravasation. Disruption of the α_Mβ₂-integrin/MMP-9 complex by integrin-(HFDDDE and DDGW) and MMP-9-(CTT and CRV) binding peptides strongly reduced PMN migration in vitro and in vivo.