SREERAMKUMAR et al: ESL-1 IN INFLAMMATORY AND PROGENITOR TRAFFICKING

Beyond its well-established roles in mediating leukocyte rolling, E-selectin is emerging as a multifunctional receptor capable of inducing integrin activation in neutrophils, and of regulating various biological processes in hematopoietic precursors. While these effects suggest important homeostatic contributions of this selectin in the immune and hematological systems, the ligands responsible for transducing these effects in different leukocyte lineages are not well defined. We have characterized mice deficient in ESL-1, or in both PSGL-1 and ESL-1, to explore and compare the contributions of these glycoproteins in immune and hematopoietic cell trafficking. In the steady-state, ESL-1 deficiency resulted in a moderate myeloid expansion that became more prominent when both glycoproteins were eliminated. During inflammation, PSGL-1 dominated E-selectin binding, rolling, integrin activation and extravasation of mature neutrophils, but only the combined deficiency in PSGL-1 and ESL-1 completely abrogated leukocyte recruitment. Surprisingly, we find that the levels of ESL-1 were strongly elevated in hematopoietic progenitor cells (HPC). These elevations correlated with a prominent function of ESL-1 for E-selectin binding and for migration of HPC into the bone marrow. Our results uncover dominant roles for ESL-1 in the immature compartment, and a functional shift towards PSGL-1-dependence in mature neutrophils. For personal use only. on October 28, 2017. by guest www.bloodjournal.org From