Prolactin increases the susceptibility of primary leukemia cells to NK and LAK effectors.
Our previous studies have shown that prolactin (PRL), a pituitary and lymphocyte hormone and a ligand of the cytokine/hemopoietin receptors (R) superfamily, acts synergistically with interleukin (IL)-2 on the development of lymphokine activated killer (LAK) cells and enhances the effects of GM-CSF and IL-3 on myeloid progenitors' proliferation and differentiation. More recently, we have demonstrated that GM-CSF and IL-3 increase the sensitivity of acute myeloid leukemic (AML) cells to LAK activity. Together, these findings have prompted us to study the role of PRL on the target arm of the LAK response. We show here that CD33+ blasts from AML patients express membrane PRL-R and that the PRL/PRL-R interaction is followed by increased susceptibility to natural killer (NK) (p < 0.02) and LAK (p < 0.001) cells. As predicted from the dimerization model of PRL-R and in agreement with previous reports, the response of AML blasts to PRL was bell-shaped with a trend peak at 25 ng/ml. Although enhanced lysis occurred at the target recognition level, it was not accompanied by changes in the MHC class I, cellular adhesion molecules, or myeloid differentiation antigens. Cell cycle recruitment and lysis increased concurrently in three cases studied, suggesting a modulatory action of PRL on the expression of putative cycle-related NK/LAK-target structures. Together, these data strengthen the role of PRL in the LAK response.
Oberholtzer
E
E
Department of Internal Medicine, University of Turin, Italy.
Contarini
M
M
Veglia
F
F
Cossarizza
A
A
Franceschi
C
C
Geuna
M
M
Provinciali
M
M
Di Stefano
G
G
Sissom
J
J
Brizzi
M F
MF
Pegoraro
L
L
Matera
L
L
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D011388:Prolactin / Q000276:immunology* / Q000502:physiology*; D011981:Receptors, Prolactin / Q000096:biosynthesis; D063268:Sialic Acid Binding Ig-like Lectin 3; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D015815:Cell Adhesion Molecules; D011981:Receptors, Prolactin; D063268:Sialic Acid Binding Ig-like Lectin 3; D011388:Prolactin