Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P75/AIRM1 is a recently identified surface molecule that belongs to the sialoadhesin family and displays homology with the myeloid cell antigen CD33. In lymphoid cells, p75/AIRM1 is confined to natural killer cells and mediates inhibition of their cytolytic activity. In this study, we show that p75/AIRM1 is also expressed by cells of the myelomonocytic cell lineage, in which it appears at a later stage as compared with CD33. In vitro proliferation and differentiation of cord blood-derived CD34(+) cells (induced by stem cell factor and granulocyte-macrophage colony-stimulating factor) were consistently inhibited by the addition of anti-p75/AIRM1 mAb. Engagement of CD33 led to inhibition in some experiments. A sharp decrease of cell proliferation/survival was detected in all three p75/AIRM1+ chronic myeloid leukemias analyzed when cultured in the presence of either anti-p75/AIRM1 or anti-CD33 mAbs. Thus, the present study suggests that p75/AIRM1 and CD33 may play a regulatory role in normal myelopoiesis and may be viewed as suitable target molecules to counteract the proliferation/survival of chronic myeloid leukemias.
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PMID:Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or leukemic myeloid cells. 1061 43

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.
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PMID:p75/AIRM1 and CD33, two sialoadhesin receptors that regulate the proliferation or the survival of normal and leukemic myeloid cells. 1151 47