Evidence for a novel function of E-selectin in neutrophil recruitment unrelated to leukocyte rolling

C. L. Ramos, E. J. Kunkel, U. Jung, C. R. Norton, K. W. McIntyre, K. M. Gillooly, M. B. Lawrence, D. Vestweber, B. A. Wolitzky, K. Ley

Research output: Contribution to journalArticlepeer-review

Abstract

The functional effects of three monoclonal antibodies (mAbs) raised against murine E-selectin, 9A9, 10E6 and IOE9.6, on neutrophil recruitment, leukocyte rolling and circulating leukocyte concentrations in vivo, as well as adhesion of myeloid cells to E-selectin transfectants and recombinant E-selectin-IgG fusion protein in vitro were investigated. MAbs 9A9 and 10E6 map to the lectin and EGF-like domains of murine E-selectin, while mAb 10E9.6 binds to the consensus repeat region. IOE9.6 blocked neutrophil recruitment to peritonitis induced by injection of thioglycollate into Balb/c mice by more than 90%, while 9A9 and 10E6 showed only partial effects (<50% inhibition). Neither 9A9 nor IOE9.6 alone blocked leukocyte rolling in TNF-o treated venules of Balb/c mice, but 9A9 almost completely inhibited leukocyte rolling when combined with the function-blocking murine P-selectin mAb, RB40.34. In contrast, 10E9.6 had no effect on leukocyte rolling in RB40.34-treated Balb/c or C57BL/6 mice. 10E9.6 did not affect adhesion of myeloid cells to Eselectin transfectants nor attachment, rolling and detachment of myeloid cells to murine E-selectin-IgG fusion protein. However, adhesion was completely blocked in the same assays by 9A9. Taken together, these results indicate that E-selectin serves a function, other than rolling, that may be critically important for neutropohil recruitment to inflammatory sites in Balb/c mice. Supported in part by NIH HL54136 and HL07284.

Original languageEnglish (US)
Pages (from-to)A610
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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