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Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor

Garner, Leslie B ; Willis, Monte S ; Carlson, Deborah L ; DiMaio, J. Michael ; White, Michael D ; White, D. Jean ; Adams, Glenn A., IV ; Horton, Jureta W ; Giroir, Brett P

American journal of physiology. Heart and circulatory physiology, 2003-12, Vol.285 (6), p.H2500-H2509 [Periódico revisado por pares]

United States

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  • Título:
    Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor
  • Autor: Garner, Leslie B ; Willis, Monte S ; Carlson, Deborah L ; DiMaio, J. Michael ; White, Michael D ; White, D. Jean ; Adams, Glenn A., IV ; Horton, Jureta W ; Giroir, Brett P
  • Assuntos: Animals ; Antibodies ; Gene Expression - immunology ; Heart Diseases - immunology ; Heart Diseases - metabolism ; Heart Diseases - physiopathology ; Lipopolysaccharides - pharmacology ; Macrophage Migration-Inhibitory Factors - blood ; Macrophage Migration-Inhibitory Factors - genetics ; Macrophage Migration-Inhibitory Factors - immunology ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Myocardium - cytology ; Myocardium - metabolism ; Myocytes, Cardiac - metabolism ; RNA, Messenger - metabolism ; Sepsis - immunology ; Sepsis - metabolism
  • É parte de: American journal of physiology. Heart and circulatory physiology, 2003-12, Vol.285 (6), p.H2500-H2509
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: 1 Department of Pediatrics, University of Texas Southwestern, Dallas 75390-9063; 2 Department of Surgery, University of Texas Southwestern, Dallas 75390-9160; 3 Department of Pathology, University of Texas Southwestern, Dallas 75390-9072; and 4 Department of Cardiothoracic Surgery, University of Texas Southwestern, Dallas, Texas 75390-9130 Submitted 8 May 2003 ; accepted in final form 20 August 2003 Macrophage migration inhibitory factor (MIF) is a pluripotent proinflammatory cytokine that is ubiquitously expressed in organs, including the heart. However, no specific role for MIF in modulating cardiac performance has yet been described. Therefore, we examined cardiac MIF expression in mice after LPS challenge (4 mg/kg) and tested the hypothesis that MIF is a mediator of LPS-induced cardiac dysfunction. Western blots of whole heart lysates, as well as immunohistochemistry, documented constitutive MIF protein expression in the heart. Cardiac MIF protein levels significantly decreased after LPS challenge, reaching a nadir at 12 h, and then returned to baseline by 24 h. This pattern was consistent with MIF release from cytoplasmic stores after endotoxin challenge. After release of protein, MIF mRNA levels increased 24–48 h postchallenge. To determine the functional consequences of MIF release, we treated LPS-challenged mice with anti-MIF neutralizing antibodies or isotype control antibodies. Anti-MIF-treated animals had significantly improved cardiac function, as evidenced by a significant improvement in left ventricular (LV) fractional shortening percentage at 8, 12, 24, and 48 h after endotoxin challenge. In support of these findings, perfusion of isolated beating mouse hearts (Langendorff preparation) with recombinant MIF (20 ng/ml) led to a significant decrease in both systolic and diastolic performance [LV pressure (LVP), positive and negative first derivative of LVP with respect to time, and rate of LVP rise at developed pressure of 40 mmHg]. This study demonstrates that MIF mediates LPS-induced cardiac dysfunction and suggests that MIF should be considered a pharmacological target for the treatment of cardiac dysfunction in sepsis and potentially other cardiac diseases. cardiac dysfunction; innate immunity; sepsis; lipopolysaccharide Address for reprint requests and other correspondence: B. P. Giroir, Dept. of Pediatrics, Univ. of Texas Southwestern, 5323 Harry Hines Blvd., Dallas, TX 75390-9063 (E-mail: brett.giroir{at}childrens.com ).
  • Editor: United States
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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