Fpr2/3 governs LXA₄biosynthesis and downstream inflammatory responses in the microcirculation during ischemia and reflow. Ischemic episodes led to an Fpr2/3-mediated formation of platelet/PMN aggregates, with a signal starting from the receptor expressed on the leukocyte. Aggregates afford the transcellular biosynthesis of LXA₄ via the concerted action of 5-lipoxygenase (5-LOX) and 12/15-LOX, in PMN and platelet, respectively. High levels of LXA₄ assured an appropriate (physiological) vascular inflammation during reperfusion (that subsides within 3-4 hours; not shown). Inappropriate aggregate formation during ischemia leads to low LXA₄ levels, with consequent higher degree of leukocyte adhesion and extravasation during reperfusion (reflow). The effector functions of LXA₄ on vascular inflammation processes are also mediated by Fpr2/3, because they are absent in mice deficient for this receptor. Among several mechanisms, acetylation of cyclo-oxygenase-2 (COX2) by ASA jumpstarts this protective circuit, with formation of 15-epi-LXA₄, activating Fpr2/3 and moderating vascular reactivity. In summary, mouse Fpr2/3 and, we propose its human counterpart ALX/FPR2, governs the extent of vascular inflammation in conditions of occlusion and reflow, by promoting formation of LXA₄, and also mediating the direct effects of this bioactive lipid mediator on leukocyte adhesion and emigration.