Prolactin stimulates integrin-mediated adhesion of circulating mononuclear cells to endothelial cells

Abstract

Attachment of leukocytes to endothelial cells is an essential step for the extravasation and recruitment of cells at sites of inflammation. The pituitary hormone prolactin (PRL) is involved in the inflammatory process. Here, we show that treatment with PRL of human peripheral blood mononuclear cells (PBMC) stimulates their adhesion to human umbilical vein endothelial cells (HUVEC) activated by interleukin-1b. Stimulation of adhesion by PRL is mediated via integrins leukocyte functional antigen-1 (LFA-1) and very late antigen-4 (VLA-4), because immunoneutralization of both integrins prevents PRL action. Also, PRL promotes the adhesion of PBMC to immobilized intercellular adhesion molecule-1 and fibronectin, ligands for LFA-1 and VLA-4, respectively. Stimulation of integrin-mediated cell adhesion by PRL may involve the activation of chemokine receptors, because PRL upregulates the expression of the G-protein-coupled chemokine receptor CXCR3 in PBMC, and pertussis toxin, a specific G-protein inhibitor, blocks PRL stimulation of PBMC adhesion to HUVEC. In addition, PRL stimulates tyrosine phosphorylation pathways leading to leukocyte adhesion. PRL triggered the tyrosine phosphorylation of Janus kinase-2, of signal transducer and activator of transcription-3 and 5, and of the focal adhesion protein paxillin. Furthermore, genistein, a tyrosine kinase inhibitor, blocked PRLstimulated adhesion of PBMC and Jurkat T-cells to HUVEC. These results suggest that PRL promotes integrinmediated leukocyte adhesion to endothelial cells via chemokine receptors and tyrosine phosphorylation signaling pathways.

Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells

“…In the present study, we identify a novel PRL-dependent interaction between the serine/threonine kinase Nek3 and paxillin (Figure 5a). Although paxillin has been shown to be tyrosine phosphorylated in response to PRL stimulation (Canbay et al, 1997;Montes et al, 2005), the data presented in this study are the first report of paxillin serine phosphorylation in response to PRL stimulation. Untransfected and control siRNA T47D transfected (Figure 5b and data not shown) showed a significant increase in paxillin serine phosphorylation in the presence of PRL.…”

Prolactin Levels and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women

“…9 In addition, in vitro studies show that prolactin stimulates integrin-mediated adhesion of circulating mononuclear cells to endothelium and induces vascular smooth muscle cell proliferation. 10,11 Altogether, these results suggest that prolactin may contribute to a higher cardiovascular risk profile and, simultaneously, may have an effect on the various components within the atherosclerotic lesion.…”

Prolactin and Preclinical Atherosclerosis in Menopausal Women With Cardiovascular Risk Factors

“…29 Because prolactin affects most of these newly introduced mechanisms after menopause, 30,31 we may speculate that, although circulating levels decrease with time, variations may remain physiologically relevant and may augment mechanisms mediating hypertension. Prolactin may increase arterial stiffness through changes in vascular tone, induction of low-grade inflammation, and smooth muscle cell proliferation [32][33][34][35][36] and may, thus, influence central and peripheral hemodynamics. Because prolactin is considered a hormone associated with stress, 37 mental stress may be a potential mechanism linking higher levels of this hormone with high blood pressure.…”