The 130-kDa glycoform of CD43 functions as an E-selectin ligand for activated Th1 cells in vitro and in delayed-type hypersensitivity reactions in vivo.
Selectins are carbohydrate-binding molecules involved in constitutive lymphocyte homing and chronic and acute inflammation processes. Th1 lymphocytes participate in cell-mediated inflammatory reactions, where the selectins play a role and predominate in delayed-type hypersensitivity (DTH) reactions of the skin. Of the many candidate ligands for selectins, only P-selectin glycoprotein ligand 1 (PSGL-1), which also acts as an E-selectin ligand, has been characterized extensively at molecular, cellular, and functional levels on T cells. Here, we report that the glycosylated form of CD43 expressed in Th1 cells is a functional E-selectin-specific ligand in vitro. Furthermore, we have generated PSGL-1(-/-)/CD43(-/-) double-deficient mice (double knockout (DKO)) to demonstrate the relevance of CD43 as an E-selectin ligand in vitro and in vivo. Under flow conditions, DKO Th1 cells exhibited impaired E-selectin binding as compared with wild-type, PSGL-1(-/-), or CD43(-/-) Th1 cells. DKO mice also showed diminished ear inflammation in response to dinitrofluorobenzene-induced DTH that correlated with a reduced number of T cells in infiltrates in the challenged ear. These results demonstrate that both PSGL-1 and CD43 are major E-selectin ligands and are likely to be important during leukocyte recruitment in the development of inflammatory reactions.
Alcaide
Pilar
P
Department of Pathology, Center for Excellence in Vascular Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
King
Sandra L
SL
Dimitroff
Charles J
CJ
Lim
Yaw-Chyn
YC
Fuhlbrigge
Robert C
RC
Luscinskas
Francis W
FW
D000818:Animals; D019040:E-Selectin / Q000502:physiology*; D006031:Glycosylation; D006968:Hypersensitivity, Delayed / Q000209:etiology*; D051917:Leukosialin / Q000502:physiology*; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology*
D019040:E-Selectin; D051917:Leukosialin; D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein