Cardiac dysfunction induced by experimental myocardial infarction impairs the host defense response to bacterial infection in mice because of reduced phagocytosis of Kupffer cells.
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-gamma 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.
Nogami
Yashiro
Y
Department of Surgery, National Defense Medical College, Saitama, Japan.
Kinoshita
Manabu
M
Takase
Bonpei
B
Inatsu
Akihito
A
Ishihara
Masayuki
M
Seki
Shuhji
S
Maehara
Tadaaki
T
D000818:Animals; D002097:C-Reactive Protein / Q000008:administration & dosage; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000276:immunology*; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000097:blood; D020382:Interleukin-18 / Q000008:administration & dosage; D007728:Kupffer Cells / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000276:immunology / Q000503:physiopathology*; D010587:Phagocytosis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000276:immunology / Q000503:physiopathology*; D016277:Ventricular Function, Left
D007075:Immunoglobulin M; D018836:Inflammation Mediators; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002097:C-Reactive Protein