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 expressed 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 the marrow compartment is unclear. In this study, marrow cells from normal and acute leukaemic donors, as well as leukaemic cell lines, were cultured in the presence of various monoclonal antibodies (mAbs) to ICAM-3, and apoptosis 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 intact 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 interactions, 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.
Stucki
A
A
Clinical Research Division, Fred Hutchinson Cancer Research Center, the Department of Medicine, University of Washington, Seattle, WA, USA.
Hayflick
J S
JS
Sandmaier
B M
BM
D000911:Antibodies, Monoclonal / Q000378:metabolism*; D015703:Antigens, CD; D000943:Antigens, Differentiation; D017209:Apoptosis / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D011961:Receptors, Fc / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D011961:Receptors, Fc; D018124:Receptors, Tumor Necrosis Factor