A splenic reservoir of pro-angiogenic neutrophils supports blood flow recovery after peripheral tissue ischemia

CD49d+CXCR4hiVEGFR1hi pro-angiogenic neutrophils rapidly accumulate in ischemic mouse hindlimb muscle and their mobilization from the spleen supports blood flow recovery.

• Why it matters: Neutrophil subsets that promote angiogenesis are linked to ischemic recovery, but their origin and recruitment mechanisms—especially the role of extramedullary reservoirs—are unclear.
• What they did: In mice with hindlimb ischemia, spectral flow cytometry and immunohistochemistry tracked PANs, while blood flow recovery was measured by laser speckle flowmetry; splenectomy and sympathectomy with 6-OHDA, plus splenic denervation, tested mobilization via CXCL12/CXCR4 retention.
• The result: PANs were maintained in a splenic reservoir and released after ischemia through sympathetic activation that reduced CXCL12 in splenic red pulp; in humans during elective abdominal aortic aneurysm repair, a similar PAN phenotype increased rapidly after lower limb ischemia.