title: BNP directly immunoregulates the innate immune system of cardiac transplant recipients in vitro.
abstract: BACKGROUND
  The innate immune system plays an important role in cardiac allograft rejection. BNP has frequently been reported to elevate during acute cardiac rejection, yet the explanation behind this phenomenon is unclear. We hypothesized that BNP might interact with the innate immune system in cardiac transplant recipients and devised a series of in vitro culture experiments to explore this phenomena.
  
  
  METHODS
  PBMCs were isolated from whole blood of (total n = 40) cardiac transplant recipients. Short (24h, n = 20) and long term (72h, n = 20) co-cultures of innate cells in the presence or absence of BNP were performed. BNP was added at two specific concentrations and compared to placebo control. Innate cells were immunophenotyped using flow cytometry.
  
  
  RESULTS
  BNP dose dependently reduced the total number of monocytes, B cells and NK cells. Furthermore, BNP co-culture impaired NK cell cytotoxicity and adhesion of non-classical monocytes (via down-regulation of CD11c).
  
  
  CONCLUSIONS
  BNP has an additional physiological role of moderating components of the innate immune system. Although speculative, this could be beneficial to cardiac transplant recipients as the innate immune system is involved in allograft rejection. Further investigation is required to elucidate the mechanism behind how BNP affects immune cells and whether the same effects are consistent with the adaptive immune system.
authors.affiliation: North West Regional Cardiac and Transplant Unit, University of South Manchester NHS Foundation Trust, Wythenshawe Hospital, Manchester, United Kingdom. doctorshaw@doctors.org.uk
authors.forename: S M
authors.initials: SM
authors.lastname: Shaw
authors.forename: J E
authors.initials: JE
authors.lastname: Fildes
authors.forename: C M
authors.initials: CM
authors.lastname: Puchałka
authors.forename: M
authors.initials: M
authors.lastname: Basith
authors.forename: N
authors.initials: N
authors.lastname: Yonan
authors.forename: S G
authors.initials: SG
authors.lastname: Williams
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D045283:Natriuretic Agents / Q000494:pharmacology*; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D012015:Reference Standards
chemical_list: D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain