p75/AIRM1 and CD33, two sialoadhesin receptors that regulate the proliferation or the survival of normal and leukemic myeloid cells.
Inhibitory receptors originally identified in natural killer (NK) cells have also been detected in other leukocyte types, thus suggesting that they may play a more general role in the control of leukocyte function. Here we report data on p75/adhesion receptor molecule 1 (AIRM1), a surface inhibitory receptor of the sialoadhesin family originally identified in NK cells that is also expressed by normal and leukemic myeloid cells. Given the homology between p75/AIRM1 and CD33, we also reanalyzed CD33, a major myeloid marker of still unknown function. We discuss recent data indicating that engagement of p75/AIRM1 or CD33 sharply inhibits the in vitro proliferation/differentiation of CD34+ myeloid precursors induced by stem cell factor and granulocyte-macrophage colony-stimulating factor. Importantly, a similar in vitro inhibitory effect occurs in monocyte/macrophages as well as in chronic or acute myeloid leukemias. While CD33 appears to act via the induction of apoptosis, p75/AIRM1 blocks cell proliferation but does not appear to induce apoptosis. A synergistic effect in the induction of apoptosis has also been documented between antibodies specific for CD33 and the chemotherapic agent etoposide. Taken together, the use of appropriate ligands against CD33 or p75/AIRM1 may represent a new therapeutic tool for treatment of myeloid leukemias or diseases characterized by overwhelming macrophage activation.
Mingari
M C
MC
Istituto Nazionale per la Ricerca sul Cancro, Centro Biotecnologie Avanzate, Genova, Italy.
Vitale
C
C
Romagnani
C
C
Falco
M
M
Moretta
L
L
D015703:Antigens, CD / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003432:Cross-Linking Reagents; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology*; D011971:Receptors, Immunologic / Q000502:physiology*; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D003432:Cross-Linking Reagents; D011971:Receptors, Immunologic; D063268:Sialic Acid Binding Ig-like Lectin 3; C121772:adhesion inhibitory receptor molecule 1