Targeted Deletion of HIF-1α Gene in T Cells Prevents their Inhibition in Hypoxic Inflamed Tissues and Improves Septic Mice Survival (original) (raw)
Figure 1
Increased survival and decreased bacterial sepsis-associated tissue damage of mice with T-cell targeted deletion of HIF-1α.
A: Use of the hypoxic marker EF5 reveals that CD4+ and CD8+ T cells have been exposed to low oxygen tension (hypoxic) conditions in the peritoneum during sepsis in mice. Single cell suspensions from peritoneal lavage fluid and spleens were analyzed by flow cytometry using anti-EF5 mAb (Elk3-52 Cy5). B: High Efficiency of Cre recombinase-mediated deletion of HIF-1 α in T-Cells. Efficiency of deletion was calculated by quantitative real-time PCR as described. Constitutively synthesized HIF-1 α mRNA was detected in control (lck-Cre negative) but not in (lck-Cre positive) HIF1 α gene targeted mice. N = 3 per group. C: T cell lineage specific HIF-1 α deficient mice are more resistant to lethal sepsis after cecal ligation and puncture procedure. Mice underwent CLP and were observed for mortality. N = 13 per group. p = 0.0326, Logrank (Mantel-Cox). D: T cell lineage specific HIF-1 α deficient mice have less sepsis-associated liver damage as evaluated by levels of ALT transaminase activity in serum. Serum samples obtained from mice 72 hrs after CLP. *:p<0.05 vs. WT, N = 5–6 per group.