Figure 4.

Schematic illustration of the signaling pathways and mechanisms that help control phagocyte migration and abundance during larval zebrafish acute tail fin injury. (A) A gradient of H₂O₂, generated at the wound margin, is sensed by neutrophils through oxidation of Lyn, leading to directed neutrophil migration (1). Neutrophil-delivered Mpx consumes H₂O₂ producing hypochlorous acid (HOCl) (2). (B) Macrophage arrival at the wound site is promoted by NADPH oxidase activity and Yrk, in addition to Cxcr3.2/Cxcl11(1). In this context, Cxcr3.3 acts as a scavenger receptor to negatively regulate Cxcr3.2 function. Macrophage-delivered PGE2 promotes neutrophil retrograde chemotaxis (2) together with NADPH/Yrk-dependent contact-mediated guidance from macrophages (3). Cxcr2 signaling also contributes to initiate neutrophil retrograde chemotaxis (4). (C) Cxcr4/Cxcl12 signaling contributes to the retention of neutrophils at the wound site (1) along with Hif-1 activation (2). Macrophages at the wound site also remove apoptotic neutrophil debris (3).