Figure 1.

Neutrophil migration during inflammation and sepsis is defective in GEF-H1−/− mice. (A) Mice underwent sham (n = 3) or received an intraperitoneal injection of 3% TGA (GEF-H1+/+, n = 6; GEF-H1−/−, n = 5), and neutrophil yields in the peritoneum were determined 5 h later. Mean values ± SEM are shown. (B) Bone marrow–derived neutrophils were isolated from GEF-H1+/+ and GEF-H1−/− mice and transferred by tail vein injection into wild-type recipient mice. Thioglycolate peritonitis (Thio) was induced at the time of neutrophil transfer, and the peritoneum was lavaged 5 h after injection. Ratios of CFSEhi GEF-H1−/− donor cells to CFSElo GEF-H1+/+ donor cells were determined (n = 5) and normalized to pretransfer ratios. Data are shown as mean ± SEM. (C) Mice underwent CLP-induced sepsis, and the peritoneum was lavaged 12 h after. Mean neutrophil yields are shown ± SEM. (D) GEF-H1+/+ (n = 8) and GEF-H1−/− (n = 12) mice underwent CLP surgery, and survival was monitored every 12 h for 1 wk. A p-value was determined using the log-rank Mantel–Cox test. (E) Hematopoietically reconstituted mice were generated as described in Materials and methods. 12 wk after reconstitution, GEF-H1+/+ (n = 6) and GEF-H1−/− (n = 6) chimeric mice underwent CLP surgery, and survival was monitored every 12 h for 10 d. A p-value was determined using the log-rank Mantel–Cox test.

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