Cardiac dysfunction in StrepTSS: group A streptococcus disrupts the directional cardiomyocyte-to-macrophage crosstalk that maintains macrophage quiescence.
Cytokine
; 59(1): 191-4, 2012 Jul.
Article
in En
| MEDLINE
| ID: mdl-22534112
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-1ß, 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Shock, Septic
/
Streptococcus pyogenes
/
Myocytes, Cardiac
/
Heart
/
Macrophages
Limits:
Animals
Language:
En
Journal:
Cytokine
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2012
Document type:
Article
Affiliation country:
United States