TY - JOUR
T1 - Role of prolactin in the in vitro development of interleukin-2-driven anti-tumoural lymphokine-activated killer cells
AU - Matera, L.
AU - Bellone, G.
AU - Lebrun, J. J.
AU - Kelly, P. A.
AU - Hooghe Peters, E. L.
AU - Francia Di Celle, P.
AU - Foa, R.
AU - Contarini, M.
AU - Avanzi, G.
AU - Asnaghi, V.
PY - 1996
Y1 - 1996
N2 - Exogenous prolactin (PRL) has been shown to synergize with low-dose interleukin-2 (IL-2) and induce the proliferation and lymphokine-activated killer (LAK) maturation of natural killer (NK) cells. PRL itself can also generate LAK activity. Here we show that its local production occurs during, and is necessary for, LAK development. IL-2-stimulated peripheral blood mononuclear cells (PBMC) and purified NK cells were exposed to anti-human (h)PRL antiserum, and residual LAK activity was measured on day 7 against the promyelocytic leukaemia cell line HL-60. Inhibition of LAK activity was much more evident in PBMC compared with NK cell cultures (47% decrease, P = 0.013 and 18.5% decrease, P = 0.048, respectively). Up-modulation of a 32S-methionine-labelled 27 000 MW protein was detected in the lysates and supernatants of IL2-stimulatcd PBMC immunoprecipitated with an anti-PRL antiserum. By contrast, the cytoplasmic PRL immunoreactivity observed in freshly isolated NK cells and in IL-2-stimulated, but not unstimulated, NK cell cultures was not associated with PRL gene activation, and can thus be referred to internalized PRL. Preferential re-uptake of externally derived PRL by IL-2 stimulated NK cells was also indicated by up-modulation of the PRL receptor. These data, as a whole, indicate that the PRL promotion of LAK differentiation is mainly mediated by paracrine secretion, with a minor contribution from internalized PRL.
AB - Exogenous prolactin (PRL) has been shown to synergize with low-dose interleukin-2 (IL-2) and induce the proliferation and lymphokine-activated killer (LAK) maturation of natural killer (NK) cells. PRL itself can also generate LAK activity. Here we show that its local production occurs during, and is necessary for, LAK development. IL-2-stimulated peripheral blood mononuclear cells (PBMC) and purified NK cells were exposed to anti-human (h)PRL antiserum, and residual LAK activity was measured on day 7 against the promyelocytic leukaemia cell line HL-60. Inhibition of LAK activity was much more evident in PBMC compared with NK cell cultures (47% decrease, P = 0.013 and 18.5% decrease, P = 0.048, respectively). Up-modulation of a 32S-methionine-labelled 27 000 MW protein was detected in the lysates and supernatants of IL2-stimulatcd PBMC immunoprecipitated with an anti-PRL antiserum. By contrast, the cytoplasmic PRL immunoreactivity observed in freshly isolated NK cells and in IL-2-stimulated, but not unstimulated, NK cell cultures was not associated with PRL gene activation, and can thus be referred to internalized PRL. Preferential re-uptake of externally derived PRL by IL-2 stimulated NK cells was also indicated by up-modulation of the PRL receptor. These data, as a whole, indicate that the PRL promotion of LAK differentiation is mainly mediated by paracrine secretion, with a minor contribution from internalized PRL.
UR - http://www.scopus.com/inward/record.url?scp=10544237682&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2567.1996.d01-773.x
DO - 10.1046/j.1365-2567.1996.d01-773.x
M3 - Article
SN - 0019-2805
VL - 89
SP - 619
EP - 626
JO - Immunology
JF - Immunology
IS - 4
ER -