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Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, Virginia 22908
To study
selectin-independent leukocyte recruitment and the role of
intercellular adhesion molecule-1 (ICAM-1), we generated mice lacking
all three selectins and ICAM-1 (E/P/L/I
/
) by bone marrow
transplantation. These mice were viable and appeared healthy under
vivarium conditions, although they showed a 97% reduction in leukocyte
rolling, a 63% reduction in leukocyte firm adhesion, and a 99%
reduction of neutrophil recruitment in a thioglycollate-induced model
of peritonitis at 4 and 24 h. Mononuclear cell recruitment was
almost unaffected. All residual leukocyte rolling and most leukocyte
adhesion in these mice depended on
4-integrins, but a
small number of leukocytes (6% of wild-type control) still became adherent in the absence of all known rolling mechanisms (E-, P-, L-selectin and
4-integrins). A striking similarity of
leukocyte adhesion efficiency in E/P/L
/
and E/P/I
/
mice
suggests a pathway in which leukocyte rolling through L-selectin
requires ICAM-1 for adhesion and recruitment. Comparison of our data
with mice lacking individual or other combinations of adhesion
molecules reveal that elimination of more adhesion molecules further
reduces leukocyte recruitment but the effect is less than additive.
neutrophil adhesion; thioglycollate-induced peritonitis; intravital
microscopy; knockout mice;
4-integrins
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