| Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor. | |
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MedLine Citation:
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PMID: 12946935 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Leslie B Garner; Monte S Willis; Deborah L Carlson; J Michael DiMaio; Michael D White; D Jean White; Glenn A Adams; Jureta W Horton; Brett P Giroir |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2003-08-28 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 285 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2003 Dec |
Date Detail:
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Created Date: 2003-11-17 Completed Date: 2003-12-24 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2500-9 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, University of Texas Southwestern, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies Gene Expression / immunology Heart Diseases / immunology, metabolism*, physiopathology Lipopolysaccharides / pharmacology Macrophage Migration-Inhibitory Factors / blood*, genetics, immunology Mice Mice, Inbred C3H Mice, Inbred C57BL Myocardium / cytology, metabolism* Myocytes, Cardiac / metabolism RNA, Messenger / metabolism Sepsis / immunology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01-GM-58863/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Lipopolysaccharides; 0/Macrophage Migration-Inhibitory Factors; 0/RNA, Messenger |
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