Selectin-independent leukocyte rolling and adhesion in mice deficient in E-, P-, and L-selectin and ICAM-1

To study selectin-independent leukocyte recruitment and the role of interce llular adhesion molecule-1 (ICAM-1), we generated mice lacking all three se lectins and ICAM-1 (E/P/L/I-/-) by bone marrow transplantation. These mice were viable and appeared healthy under vivarium conditions, although they s howed a 97% reduction in leukocyte rolling, a 63% reduction in leukocyte fi rm adhesion, and a 99% reduction of neutrophil recruitment in a thioglycoll ate-induced model of peritonitis at 4 and 24 h. Mononuclear cell recruitmen t was almost unaffected. All residual leukocyte rolling and most leukocyte adhesion in these mice depended on alpha (4)-integrins, but a small number of leukocytes (6% of wild-type control) still became adherent in the absenc e of all known rolling mechanisms (E-, P-, L-selectin and alpha (4)-integri ns). 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-sele ctin requires ICAM-1 for adhesion and recruitment. Comparison of our data w ith mice lacking individual or other combinations of adhesion molecules rev eal that elimination of more adhesion molecules further reduces leukocyte r ecruitment but the effect is less than additive.