LPS pretreatment ameliorates peritonitis-induced myocardial inflammation and dysfunction: role of myocytes.
Peritonitis induced by cecal ligation and puncture (CLP) produces a systemic inflammatory response that can be largely mitigated by pretreatment of the animals with lipopolysaccharide (LPS tolerance). Although cells of myeloid origin and endothelial cells have been shown to contribute to the development of LPS tolerance, little is known regarding the potential role of parenchymal cells in this phenomenon. The major aim of the present study was to assess whether cardiac parenchymal cells (myocytes) contribute to the development of LPS tolerance. Six hours after induction of CLP rats were neutropenic and acidotic, the myocardium contained a leukocyte infiltrate [myeloperoxidase (MPO) activity was increased], and myocardial contractile function was impaired (left ventricular developed pressure was decreased). In animals that were pretreated with LPS these manifestations of sepsis were largely reversed. Further studies focused on the responses of cardiac myocytes to CLP and whether myocytes contributed to the development of LPS tolerance. Myocytes were isolated from rat hearts 6 h after induction of CLP. These myocytes 1) exhibited an impaired ability to shorten in response to pacing, 2) contained the nuclear transcription factor NF-kappaB in their nuclei, 3) increased their surface levels of intercellular adhesion molecule-1 (ICAM-1), and 4) were hyperadhesive for neutrophils. All of these events did not occur in myocytes obtained from animals that were pretreated with LPS before induction of CLP. These findings indicate that LPS tolerance can be induced in myocytes with respect to polymorphonuclear leukocyte adhesion, presumably by an inability of CLP to mobilize NF-kappaB to the myocyte nuclei and, thereby, preventing an increase in surface levels of ICAM-1.
Neviere
R R
RR
Vascular Biology Program, London Health Sciences Centre-Research Incorporated, University of Western Ontario, London, Ontario, Canada N6A 4G5.
Cepinskas
G
G
Madorin
W S
WS
Hoque
N
N
Karmazyn
M
M
Sibbald
W J
WJ
Kvietys
P R
PR
D000818:Animals; D002448:Cell Adhesion; D006331:Heart Diseases / Q000503:physiopathology* / Q000517:prevention & control; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology*; D016328:NF-kappa B / Q000502:physiology; D009504:Neutrophils / Q000473:pathology; D010538:Peritonitis / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1