title: IgE receptor-mediated mast-cell renin release.
abstract: Renin is a newly discovered constituent of mast cells. Given that mast cells play a major role in IgE-mediated allergic hypersensitivity, we investigated whether activation of the high-affinity IgE receptor FcεRI elicits release of mast-cell renin. Cross-linking of FcεRI on the surface of mature bone marrow-derived mast cells elicited release of enzymatically active renin protein. The angiotensin I-forming activity of the renin protein was completely blocked by the selective renin inhibitor BILA 2157, which excludes formation of angiotensin I by proteases other than renin. FcεRI-mediated mast-cell renin release was inhibited by dexamethasone and potentiated by the proinflammatory mediator PGE2. Furthermore, cross-linking of mast-cell FcεRI in ex vivo murine hearts passively sensitized with monoclonal anti-DNP IgE also resulted in mast-cell degranulation and overflow of renin. Our findings indicate that IgE-mediated allergic hypersensitivity provokes release of renin from both cultured and resident cardiac mast cells, a process likely to be exacerbated in a chronic inflammatory background. Given the widespread distribution of mast cells, and the presence of angiotensinogen and angiotensin-converting enzyme in many tissues, renin release in immediate hypersensitivity reactions could result in local angiotensin II generation and multiorgan dysfunctions.
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, New York.
authors.forename: Silvia
authors.initials: S
authors.lastname: Aldi
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, New York.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Robador
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, New York.
authors.forename: Kengo
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Annarita
authors.initials: A
authors.lastname: Di Lorenzo
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, New York. Electronic address: rlevi@med.cornell.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Levi
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; C579617:FcepsilonRIalpha protein, mouse; D017455:Receptors, IgE; D003907:Dexamethasone; D006632:Histamine; D019009:Proto-Oncogene Proteins c-kit; D012083:Renin; D015232:Dinoprostone