Lsc KO mice have peripheral-blood leukocytosis and extramedullary hematopoiesis, with normal recruitment of neutrophils to E coli peritonitis. (A) The mean number of peripheral-blood leukocytes ± SEM in adult WT and Lsc KO mice (n = 11 age- and sex-matched mice of each genotype) (see Table 2). The mean peripheral leukocyte count in Lsc KO mice is 2-fold that of WT mice. (B) Extramedullary hematopoiesis in the red pulp of the spleen. Light micrographs (25 × objective) of spleen sections from WT and Lsc KO mice stained with hematoxylin and eosin. Representative of 4 mice of each genotype. (C) Lsc KO mice have significantly fewer peritoneal neutrophils at rest, but similar numbers of peritoneal neutrophils 12 hours after intraperitoneal injection of 10⁶ cfu E coli. Data are the mean number of peritoneal neutrophils ± SEM for at least 4 mice at each time point. (D) Model for the role of Lsc in formyl-peptide–stimulated neutrophils. Lsc is required to form a single-dominant pseudopod and for normal adhesion in formyl-peptide–stimulated neutrophils. Schematic diagram of Lsc signaling pathways in neutrophils (see “Discussion” for details). Formyl-peptides bind 7-transmembrane segment surface receptors. The ligand-bound receptors release activated G-protein α-subunits that stimulate the Lsc DH domain to activate RhoA. Activated RhoA is required to form a single-dominant pseudopod. Lsc is also required for formyl-peptide–stimulated neutrophil adhesion. Lsc may regulate adhesion through a RhoA-independent pathway. Lsc is not required for RhoA-dependent uropod release.