Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 127, Issue 8, Pages 1964-1972Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.jid.5700805
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Funding
- NHLBI NIH HHS [HL36028, HL53993] Funding Source: Medline
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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 lpSGL-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, PSGIL-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 PSGIL-1 and CD43 are major E-selectin ligands and are likely to be important during leukocyte recruitment in the development of inflammatory reactions.
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