Neutrophil depletion: beneficial or detrimental to post‐ischemic hind limb recovery in Cx40‐/‐ vs. WT mice? (670.8)

Abstract

Connexins (Cx) regulate vascular function, remodeling, and the inflammatory response in various vascular diseases. Recovery of post‐ischemic hindlimb use and perfusion is significantly impaired in mice with global deletion of Cx40 (Cx40‐/‐), and infiltrated activated macrophages were significantly more numerous in the ischemic limbs of these mice 14 days post‐injury as compared to wild type (WT) mice. Here we begin to explore whether the inflammatory response in the Cx40‐/‐ mice is detrimental to its post‐ischemic recovery process. At both 8 hours and 24 hours post‐femoral artery ligation (FAL), Cx40‐/‐ mice had a significantly larger number of infiltrated neutrophils in the ischemic gastrocnemius muscle compared to WT mice. This increased infiltration did not, however, lead to any differences in number of infiltrated activated macrophages at 3 days post‐ischemic injury in Cx40‐/‐ and WT mice. Additionally, no differences in Cx37 or Cx40 expression were detected as a consequence of ischemia in WT and Cx40‐/‐ mice, despite genotype‐specific differences in Cx37 localization. To assess the impact of excessive neutrophil infiltration on post‐ischemic recovery of limb use and perfusion, we neutrophil depleted mice by injecting 500µg of anti‐m Ly‐6G antibody (clone: RB6‐8C5) 1 day prior to, day of, and 1 day post‐surgery. Preliminary data indicate that neutrophil depletion did not significantly improve or impair recovery of limb use in WT or Cx40‐/‐ mice; however, a trend indicative of impaired limb perfusion was observed in neutrophil depleted WT, but not Cx40‐/‐ mice. These results suggest that neutrophil infiltration may support post‐ischemic recovery in WT mice, but does not improve or diminish recovery of Cx40‐/‐ mice.Grant Funding Source: Supported by HL058732