PAR2-β-arrestin signaling drives Poly(I:C)-induced monocyte/macrophage recruitment to the lungs. (A) Schematic overview of downstream PAR2 signaling pathways via recruitment of β-arrestin or G-proteins. (B) IFNα and IFNβ secreted into the cell supernatant from macrophages from F2rl1^S365A/T368A compared with WT mice on fibrinogen-coated plates. (C) Representative microscopic staining comparing the phosphorylation of ERK from peritoneal macrophage from F2rl1^S365A/T368A and WT mice after Poly(I:C) stimulation (25 μg/mL). (D) Nuclear and cytosolic quantification of pERK with Citation5. (E) Migration of macrophages and monocytes from F2rl1^S365A/T368A and WT mice on fibrinogen- or fibronectin-coated filters after Poly(I:C) stimulation (25 μg/mL). (F) Migration of macrophages from F2rl1^S365A/T368A and WT mice on fibrinogen- or fibronectin-coated filters after CpG-B stimulation (5 μM). (G) Quantification of different monocyte and macrophage subsets by flow cytometry of whole lung cell suspensions after intranasal Poly(I:C) treatment of F2rl1^S365A/T368A and WT mice. (H) Cell counts in BAL in unchallenged and Poly(I:C)-treated F2rl1^S365A/T368A and C57BL/6N mice. Mean ± SD; the 2-way ANOVA with the Sidak multiple comparison test. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. PKC, protein kinase C.