title: Cardiac dysfunction in StrepTSS: group A streptococcus disrupts the directional cardiomyocyte-to-macrophage crosstalk that maintains macrophage quiescence.
abstract: Myocardial dysfunction in group A streptococcal (GAS) toxic shock syndrome (StrepTSS) is characterized by severe biventricular dilatation and a striking reduction in ventricular performance; however, the mechanisms have not been fully elucidated. We have previously shown that pro-inflammatory cytokines are upregulated in the hearts of experimental animals with GAS bacteremia and that cardiomyocytes themselves as well as macrophages are the principal cytokine sources. Although macrophage-derived cytokines can clearly affect cardiac contractility, we questioned whether soluble cardiomyocyte-derived mediators might in turn affect macrophage function. Thus, we sought evidence of cardiomyocyte-to-macrophage directional cross-talk under resting versus GAS-stimulated conditions, using production of matrix metalloproteinase-9 (MMP-9) as an indicator of such signaling. Our results demonstrate that unstimulated cardiomyocytes produce a soluble inhibitor/s that maintains macrophage functional quiescence. Further, viable GAS induced production of cardiomyocyte-derived stimulator/s that overcomes quiescence and boosts macrophages production of MMP-9 and expression of pro-inflammatory cytokines (IL-1β, IL-6) and cardiodepressant factors (iNOS). Understanding the role of these cardiomyocyte-derived effectors of macrophage function (herein termed "cardiokines") in sepsis-associated cardiomyopathy may suggest new targets for therapeutic intervention.
authors.affiliation: Veterans Affairs Medical Center, Boise, ID 83702, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Amy E
authors.initials: AE
authors.lastname: Bryant
authors.forename: Tanyalak
authors.initials: T
authors.lastname: Parimon
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Stevens
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D006321:Heart / Q000503:physiopathology*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000382:microbiology; D012772:Shock, Septic / Q000382:microbiology* / Q000503:physiopathology*; D012995:Solubility; D013297:Streptococcus pyogenes / Q000502:physiology*
chemical_list: D020780:Matrix Metalloproteinase 9