GRK2-dependent CXCR2 downregulation promotes neutrophil rTEM in aged tissues.
(A–F) Young and aged mice were treated i.s. with IL-1β.
(A) Representative confocal images of cremasteric post-capillary venules (PCVs) of WT mice immunostained for CXCR2, MRP14 (neutrophils) and CD31. Arrows indicate CXCR2lo neutrophils (scale bar: 10 μm; dashed boxes delineate magnified areas).
(B) Percentage of luminal CXCR2lo neutrophils in cremasteric PCVs of EC Ackr1+/+ and EC Ackr1−/− chimeras (n = 3-5 mice/group).
(C) Generation of neutrophil Grk2+/+ and Grk2−/− chimeras.
(D–F) Young and aged chimeras as generated in (C) were treated i.s. with IL-1β.
(D) Percentage of luminal CXCR2lo neutrophils (n = 3-4 mice/group).
(E) Total neutrophil TEM events and (F) frequency of neutrophil rTEM as assessed by confocal IVM (n = 3-4 mice/group). Means ± SEM #p < 0.05, ####p < 0.0001 as compared to young, ∗p < 0.05, ∗∗∗p < 0.001 as indicated.
See also Figure S4.