Cardiac dysfunction induced by experimental myocardial infarction impairs the host defense response to bacterial infection in mice because of reduced phagocytosis of Kupffer cells

Nogami, Yashiro; Kinoshita, Manabu; Takase, Bonpei; Inatsu, Akihito; Ishihara, Masayuki; Seki, Shuhji; Maehara, Tadaaki

doi:10.1016/j.jtcvs.2009.11.005

« Previous Next »The Journal of Thoracic and Cardiovascular Surgery
Volume 140, Issue 3 , Pages 624-632.e3, September 2010

Cardiac dysfunction induced by experimental myocardial infarction impairs the host defense response to bacterial infection in mice because of reduced phagocytosis of Kupffer cells

Yashiro Nogami, MD
- Department of Surgery, National Defense Medical College, Saitama, Japan
Manabu Kinoshita, MD
- Department of Immunology and Microbiology, National Defense Medical College, Saitama, Japan
- Address for reprints: Manabu Kinoshita, MD, Department of Immunology and Microbiology, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
Bonpei Takase, MD
- Department of Intensive Care Medicine, National Defense Medical College, Saitama, Japan
Akihito Inatsu, MD
- Department of Laboratory Medicine, National Defense Medical College, Saitama, Japan
Masayuki Ishihara, PhD
- Division of Biomedical Engineering, National Defense Medical College Research Institute, Saitama, Japan
Shuhji Seki, MD
- Department of Immunology and Microbiology, National Defense Medical College, Saitama, Japan
Tadaaki Maehara, MD
- Department of Surgery, National Defense Medical College, Saitama, Japan

Received 29 April 2009; received in revised form 5 October 2009; accepted 2 November 2009. published online 08 February 2010.

Objective

This study was undertaken to investigate the effects of cardiac dysfunction induced by experimental myocardial infarction on the host defense response to bacterial infection and the role of Kupffer cells in mediating this response.

Methods

Myocardial infarction was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Mice were challenged with Escherichia coli intravenously 1, 5, and 14 days after myocardial infarction or sham operation. Thereafter, the cytokine production and the function of their Kupffer cells were assessed.

Results

Mice with myocardial infarction showed remarkable cardiac dysfunction and had a significantly lower survival than sham mice after bacterial challenge at 5 days after surgery; bacterial challenge at 1 or 14 days after surgery resulted in no difference in survival between myocardial infarction and sham mice. The phagocytic activity of Kupffer cells, assessed by fluorescein isothiocyanate microspheres, remarkably decreased in mice with myocardial infarction 5 days after surgery. Serum peaks of tumor necrosis factor and interferon-γ after bacterial challenge were also suppressed in mice with myocardial infarction at 5 days. Production of these cytokines and immunoglobulin-M from liver mononuclear cells was also impaired in mice with myocardial infarction. Enhancement of the phagocytic activity of Kupffer cells by C-reactive protein significantly improved survival after infection in mice with myocardial infarction, although neither interleukin-18 nor immunoglobulin-M treatment improved survival.

Conclusions

Cardiac dysfunction induced by myocardial infarction renders mice susceptible to bacterial infection and increases mortality because of a reduced ability of Kupffer cells to clear infectious bacteria. C-reactive protein-enhanced phagocytic activity of Kupffer cells may improve the poor prognosis after bacterial infection in mice with myocardial infarction.

CTSNet classification: 18, 22, 23, 30

Abbreviations and Acronyms: CRP, C-reactive protein, FITC, fluorescein isothiocyanate, IFN, interferon, Ig, immunoglobulin, IL, interleukin, IV, intravenously, LAD, left anterior descending, LV, left ventricular, MI, myocardial infarction, MNC, mononuclear cell, PBS, phosphate-buffered saline, TTC, triphenyltetrazolium chloride