Role of prolactin in the in vitro development of interleukin‐2‐driven anti‐tumoural lymphokine‐activated killer cells

Immunology - Tập 89 Số 4 - Trang 619-626 - 1996
Lina Matera1, Graziella Bellone2, Jean‐Jacques Lebrun3, Paul A. Kelly3, Elisabeth Peters4, Paola Francia di Celle4, Robin Foà5, M Contarini1, Gian Carlo Avanzi6, Veronica Asnaghi1
1Institute of Internal Medicine, corso A. M. Dogliotti 14, Turin,
2Department of Clinical Physiology, via Genova 3, Turin, Italy,
3INSERM U344-Endocrinologie Moléculaire, Faculté de Medecine Necker Enfants Malades, Paris, France.
4Pharmacology Department, VUB Laabeerklaan 103, Brussels, Belgium,
5Department of Biomedical Sciences and Human Oncology, via Genova 3, Turin, Italy,
6Department of Medical Science, Via Solaroli 17, Novara, Italy

Tóm tắt

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 27000MW protein was detected in the lysates and supernatants of IL‐2‐stimulated 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.

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Immunology

Tập 89 Số 4

619-626

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