Antibody engagement of intercellular adhesion molecule 3 triggers apoptosis of normal and leukaemic myeloid marrow cells

Intercellular adhesion molecule 3 (ICAM-3, CD50) is an immunoglobulin (Ig) domain-containing cell-cell adhesion receptor that binds to the lymphocyte function antigen 1 (LFA-1; CD11a/CD18) integrin. It is constitutively expre ssed on haematopoietic precursors and differentiated leucocytes, as well as on most leukaemic cells. ICAM-3/LFA-1 binding during a lymphocyte-mediated cellular immune response has been well established; however, its role in t he marrow compartment is unclear. In this study, marrow cells from normal a nd acute leukaemic donors, as well as leukaemic cell lines, were cultured i n the presence of various monoclonal antibodies (mAbs) to ICAM-3, and apopt osis was subsequently measured by annexin V binding. Anti-ICAM-3 mAb ICR 1. 1 engagement triggered increased percentages of apoptosis among normal and leukaemic marrow myeloid cells. Fab fragments of ICR 1.1 mimicked the intac t mAb, suggesting that the apoptotic signal was independent of Fc receptor interactions and did not require bivalent epitope engagement. In addition, the apoptotic signal was found to be independent of ICAM-1/LFA-1 binding in teractions, as well as Fas/FasL and tumour necrosis factor alpha (TNF-alpha )/TNF receptor-activated pathways, as neutralizing antibodies to CD11a/CD18 , Fas and TNF-alpha failed to abrogate the response.