IgE receptor-mediated mast-cell renin release. Academic Article uri icon

Overview

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.

publication date

  • November 18, 2013

Research

keywords

  • Mast Cells
  • Receptors, IgE
  • Renin

Identity

PubMed Central ID

  • PMC3906484

Scopus Document Identifier

  • 84892153262

Digital Object Identifier (DOI)

  • 10.1016/j.ajpath.2013.10.016

PubMed ID

  • 24262755

Additional Document Info

volume

  • 184

issue

  • 2