Mc. Mingari et al., p75/AIRM1 and CD33, two sialoadhesin receptors that regulate the proliferation or the survival of normal and leukemic myeloid cells, IMMUNOL REV, 181, 2001, pp. 260-268
Inhibitory receptors originally identified in natural killer (NK) cells hav
e also been detected in other leukocyte types, thus suggesting that they ma
y play a more general role in the control of leukocyte function. Here we re
port data on p75/adhesion receptor molecule I (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 marke
r of still unknown function. We discuss recent data indicating that engagem
ent of p75/AIRM1 or CD33 sharply inhibits the in vitro proliferation/differ
entiation of CD34(+) myeloid precursors induced by stem cell factor and gra
nulocyte macrophage colony-stimulating factor. importantly, a similar in vi
tro 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 induc
e apoptosis. A synergistic effect in the induction of apoptosis has also be
en documented between antibodies specific for CD33 and the chemotherapic ag
ent 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.