title: CD43 plays both antiadhesive and proadhesive roles in neutrophil rolling in a context-dependent manner.
abstract: As the first step in the recruitment of neutrophils into tissues, the cells become tethered to and roll on the vessel wall. These processes are mediated by interactions between the P- and E-selectins, expressed on the endothelial cells of the vessel wall, and their ligands, expressed on the neutrophils. Recently, we reported that CD43 on activated T cells functions as an E-selectin ligand and thereby mediates T cell migration to inflamed sites, in collaboration with P-selectin glycoprotein ligand-1 (PSGL-1), a major P- and E-selectin ligand. Here, we examined whether CD43 on neutrophils also functions as an E-selectin ligand. CD43 was precipitated with an E-selectin-IgG chimera from mouse bone marrow neutrophils. A CD43 deficiency diminished the E-selectin-binding activity of neutrophils when PSGL-1 was also deficient. Intravital microscopy showed that the CD43 deficiency significantly increased leukocyte rolling velocities in TNF-alpha-stimulated venules blocked with an anti-P-selectin mAb, where the rolling was mostly E-selectin dependent, when PSGL-1 was also absent. In contrast, in venules with trauma-induced inflammation, where the rolling was largely P-selectin dependent, the CD43 deficiency reduced leukocyte rolling velocities. Collectively, these observations suggest that CD43 generally serves as an antiadhesive molecule to attenuate neutrophil-endothelial interactions, but when E-selectin is expressed on endothelial cells, it also plays a proadhesive role as an E-selectin ligand.
authors: The 21st Century Center of Excellence Program, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors: Masanori
authors: M
authors: Matsumoto
authors: Akiko
authors: A
authors: Shigeta
authors: Masayuki
authors: M
authors: Miyasaka
authors: Takako
authors: T
authors: Hirata
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D019040:E-Selectin / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology; D036904:Leukocyte Rolling; D051917:Leukosialin / Q000502:physiology*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology*; D014699:Venules
chemical_list: D019040:E-Selectin; D051917:Leukosialin; D008024:Ligands