Characterization of a Functionally Important and Evolutionarily Weft-conserved Epitope Mapped to the Short Consensus Repeats of E-Selectin and L-Selectin

Mark A. Jutila, Gayle Watts, Bruce Walcheck, Geoffrey S. Kansas

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80 Scopus citations

Abstract

Sdectins represent a new family of adhesion molecules, expressed by leukocytes and endothelial cells, that are involved in the regulation of leukocyte traffic. Here we have characterized a new monoclonal antibody (mAb) (EI.-246) that recognizes both human leukocyte I-selectin (previously called LAM-1, LECAM-1, or gpgOMEI:14) and endothelial cell E-sdectin (previously called ELAM- 1). Eb246 recognized a 110-kD protein expressed on cells transfected with E-sdectin c.DNA and stained many postcapillary venules in inflamed human tonsil. EL-246 also stained human peripheral blood leukocytes and showed identity with anti-bsdectin mAb in two-color flow cytometric analysis. The expression of the leukocyte EI.-246 antigen was regulated in the same manner as I. selectin and EL,246 recognized anti-L-selectin mAb affinity-purified antigen in SDS/PAGE Western blot analysis. Further, L, selectin cDNA transfectants were specifically stained by EL-246. EL-246 blocked <95% of lymphocyte adhesion to peripheral lymph node high endothelial venules and <90% of neutrophil adhesion to E-sdectin transfectants. In addition to the ED246 epitope being expressed on two different human selectins, it was detected on L-selectin from a variety of different animals. Interestingly, domain mapping studies localized the Eb246 epitope to the short consensus repeat (SCR) domains of Lsdectin. EL246 is the first mAb that recognizes two different sdectins and potentially defines a functional epitope encoded by the SCR domains. Inhibitors of selectin function targeted to this region would be expected to have the added advantage of simultaneously blocking the activity of two distinct adhesion proteins involved in inflammation.

Original languageEnglish (US)
Pages (from-to)1565-1573
Number of pages9
JournalJournal of Experimental Medicine
Volume175
Issue number6
DOIs
StatePublished - Jun 1 1992

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