Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism.
Leukocytes are critical effectors of inflammation and tumor biology. Chemokine-like factors produced by such inflammatory sites are key mediators of tumor growth that activate leukocytic recruitment and tumor infiltration and suppress immune surveillance. Here we report that the endocrine peptide hormone, relaxin, is a regulator of leukocyte biology with properties important in recruitment to sites of inflammation. This study uses the human monocytic cell line THP-1 and normal human peripheral blood mononuclear cells to define a novel role for relaxin in regulation of leukocyte adhesion and migration. Our studies indicate that relaxin promotes adenylate cyclase activation, substrate adhesion, and migratory capacity of mononuclear leukocytes through a relaxin receptor LGR7-dependent mechanism. Relaxin-stimulated cAMP accumulation was observed to occur primarily in non-adherent cells. Relaxin stimulation results in increased substrate adhesion and increased migratory activity of leukocytes. In addition, relaxin-stimulated substrate adhesion resulted in enhanced chemotaxis to monocyte chemoattractant protein-1. These responses in THP-1 and peripheral blood mononuclear cells are relaxin dose-dependent and proportional to cAMP accumulation. We further demonstrate that LGR7 is critical for mediating these biological responses by use of RNA interference lentiviral short hairpin constructs. In summary, we provide evidence that relaxin is a novel leukocyte stimulatory agent with properties affecting adhesion and chemomigration.
Figueiredo
Kevin A
KA
Genetics Program and Department of Surgery, University of British Columbia, Canada.
Mui
Alice L
AL
Nelson
Colleen C
CC
Cox
Michael E
ME
D000262:Adenylyl Cyclases / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002469:Cell Separation; D018932:Chemokine CCL2 / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D007962:Leukocytes / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D015233:Models, Statistical; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide; D011994:Recombinant Proteins / Q000737:chemistry; D012065:Relaxin / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D018932:Chemokine CCL2; D008565:Membrane Proteins; D012333:RNA, Messenger; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D012065:Relaxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases