INCREASED EXPRESSION OF CD11B AND FUNCTIONAL-CHANGES IN EOSINOPHILS AFTER MIGRATION ACROSS ENDOTHELIAL-CELL MONOLAYERS

Eosinophils from sputum, nasal polyps, and bronchoalveolar lavages of asthmatics demonstrated a considerably increased CD11b expression, com pared with blood eosinophils. Furthermore, the tissue eosinophils expr essed ICAM-1 (CD54) and HLA-DR, whereas peripheral blood eosinophils d id not. In vitro migration of peripheral blood eosinophils across IL-1 -activated human umbilical vein endothelial cell monolayers caused a c onsiderable up-regulation of CD11b and CD35 expression, no induction o f ICAM-1 or HLA-DR, and a small but significant decrease in CD11a, CD2 9, and CD32 expression. These changes were only partially inducible wi th supernatants from nonactivated or IL-1-activated endothelial cells, platelet-activating factor, or a variety of recombinant cytokines. Th us, cell-cell interactions mediated by receptor-ligand binding or endo thelial cell membrane-bound mediators, rather than soluble factors, ar e responsible for the altered eosinophil surface marker expression. In deed, preparations of membrane fragments from IL-1-stimulated endothel ial cells were able to induce up-regulation of CD11b, which was not in hibitable with the platelet-activating factor antagonist WEB 2086 or a ntibodies against ELAM-1, VCAM-1, or ICAM-1. Investigation of the func tional significance of the increased CD11b expression on eosinophils r evealed only minimal changes in the adherence or transmigration capaci ty. Nevertheless, increased CD11b expression was related to an increas ed capacity to generate superoxide after stimulation with opsonized zy mosan. Thus, cell-cell interactions between eosinophils and endothelia l cells induce a considerable up-regulation of CD11b and CD35 on eosin ophils and an increased capacity to generate an oxidative burst.