Prolactin stimulates integrin-mediated adhesion of circulating mononuclear cells to endothelial cells.
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-1beta. 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 PRL-stimulated adhesion of PBMC and Jurkat T-cells to HUVEC. These results suggest that PRL promotes integrin-mediated leukocyte adhesion to endothelial cells via chemokine receptors and tyrosine phosphorylation signaling pathways.
Montes de Oca
Pável
P
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, Queretaro, Qro, Mexico.
Macotela
Yazmín
Y
Nava
Gabriel
G
López-Barrera
Fernando
F
de la Escalera
Gonzalo Martínez
GM
Clapp
Carmen
C
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
C515187:CXCR3 protein, human; D016023:Integrins; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014443:Tyrosine; D011388:Prolactin; D019833:Genistein