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Differential effect of E-selectin antibodies on neutrophil rolling and
recruitment to inflammatory sites
CL Ramos, EJ Kunkel, MB Lawrence, U Jung, D Vestweber, R Bosse, KW McIntyre, KM Gillooly, CR Norton, BA Wolitzky and K Ley
Department of Biomedical Engineering, University of Virginia Health
Sciences Center, Charlottesville 22908, USA.
The selectins are inducible adhesion molecules critically important for the
inflammatory response. We investigate here the functional effects of three
monoclonal antibodies (MoAbs) raised against murine E-selectin (9A9, 10E6,
and 10E9.6) on neutrophil recruitment in vivo, leukocyte rolling and
circulating leukocyte concentrations in vivo, and adhesion of myeloid cells
to E-selectin transfectants and recombinant E-selectin- IgG fusion protein
in vitro. MoAbs 9A9 and 10E6 map to the lectin and epidermal growth factor
(EGF)-like domains of murine E-selectin, whereas 10E9.6 binds to the
consensus repeat region. 10E9.6 blocked neutrophil recruitment in a model
of thioglycollate-induced peritonitis in Balb/c mice by more than 90% but
had no effect in C57BL/6 mice. 9A9 and 10E6 blocked neutrophil recruitment
in this assay only when combined with a P-selectin antibody, 5H1. Neither
9A9 nor 10E9.6 alone blocked leukocyte rolling in tumor necrosis
factor-alpha-treated venules of Balb/c mice, but 9A9 almost completely
inhibited leukocyte rolling when combined with the function-blocking murine
P-selectin MoAb, 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 E-selectin transfectants or 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 appears to be critically important for
neutrophil recruitment to inflammatory sites in Balb/c mice.
Volume 89,
Issue 8,
pp. 3009-3018,
04/15/1997
Copyright © 1997 by The American Society of Hematology
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