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Blood, Vol. 93 No. 12 (June 15), 1999: pp. 4387-4394

Human Immunoglobulin A Receptor (Fc&b.alpha;RI, CD89) Function in Transgenic Mice Requires Both FcR gamma  Chain and CR3 (CD11b/CD18)

Marjolein van Egmond, A.J. Hanneke van Vuuren, H. Craig Morton, Annemiek B. van Spriel, Li Shen, Frans M.A. Hofhuis, Takashi Saito, Tanya N. Mayadas, J. Sjef Verbeek, and Jan G.J. van de Winkel

From the Department of Immunology and Medarex Europe, University Medical Center Utrecht, Utrecht, The Netherlands; the Department of Immunohistochemistry and Immunopathology, University of Oslo, Oslo, Norway; the Department of Immunology and Microbiology, Dartmouth Medical School, Lebanon, NH; the Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba, Japan; and the Department of Pathology, Brigham and Women's Hospital, Boston, MA.

Even though more immunoglobulin A (IgA) is produced in humans than all other isotypes combined, relatively little is known about receptors that bind the Fc part of IgA. The myeloid IgA receptor, Fcalpha RI (CD89), triggers various effector functions in vitro, but its in vivo role remains unclear. Here, a transgenic mouse model is described in which Fcalpha RI is expressed under its own regulatory sequences. Receptor expression and regulation by cytokines was comparable to the human situation and hFcalpha RI can trigger phagocytosis and lysis of tumor cells. To analyze the contribution of the FcR gamma  chain or the beta 2 integrin CR3 (CD11b/CD18) in Fcalpha RI biological function, Fcalpha RI transgenic mice were crossed with either FcR gamma  chain -/- or CR3 -/- mice. In contrast to in vitro data, FcR gamma  chain was essential for surface expression of hFcalpha RI in vivo. Functional studies in hFcalpha RI/ gamma -/-mice were, therefore, limited. In vitro studies showed FcR gamma  chain to be necessary for phagocytosis. Neither hFcalpha RI expression nor phagocytosis, triggered via hFcalpha RI, were influenced by CR3. Remarkably, the capacity to lyse tumor targets was ablated in hFcalpha RI transgenic/ CR3-/- mice, although binding of neutrophils to tumor cells was intact. This shows a previously unrecognized importance of CR3 for hFcalpha RI-mediated antibody-dependent cellular cytotoxicity (ADCC).


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