Conceptual model of calcium regulation and integrin engagement during PMN recruitment in shear flow. (A) During rolling, release of calcium stores initiated by GPCR and PLC-β signals IP3-sensitive calciosomes that cooperate with Orai1 SOCE eliciting an upshift in β2-integrin activation via Rap-1 that is sensitive to the rapid and local release of calcium stores resulting in PMN arrest. (B) As the PMN transitions to arrest, integrin engagement under stress stabilizes a high affinity conformation, which triggers activation of PLC-γ. The additional calcium release caused by integrin engagement sustains SOCE-mediated calcium influx and reinforces signaling for strengthening of arrest. (C) Calcium signaling causes rearrangement of the actin cytoskeleton and activation of secondary messengers (PKC) necessary for shape polarization. Electrical depolarization of the membrane and refilling of calcium stores through SERCA pumps slowly diminish intracellular calcium.
