MACROPHAGE MIGRATION INHIBITORY FACTOR WITHIN THE ALVEOLAR SPACES INDUCES CHANGES IN THE HEART DURING LATE EXPERIMENTAL SEPSIS
| Autor: | Ping Wang, Hal A Skopicki, Edmund J. Miller, Kaie Ojamaa, Xinchun Lin, Christine N. Metz, Yousef Al-Abed, Tohru Sakuragi |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Chemokine
Heart Diseases medicine.medical_treatment Critical Care and Intensive Care Medicine Rats Sprague-Dawley Sepsis Mice Intensive care medicine Animals Macrophage Macrophage Migration-Inhibitory Factors Mice Inbred BALB C Respiratory Distress Syndrome Lung biology business.industry respiratory system medicine.disease Rats Intramolecular Oxidoreductases Pulmonary Alveoli Cytokine medicine.anatomical_structure Immunology Emergency Medicine biology.protein Cytokines Tumor necrosis factor alpha Macrophage migration inhibitory factor business Signal Transduction |
| Zdroj: | Shock. 24:556-563 |
| ISSN: | 1073-2322 |
| DOI: | 10.1097/01.shk.0000183238.70374.a8 |
| Popis: | Respiratory dysfunction during sepsis is common. However, although lung function can often be adequately supported, death frequently results from cardiovascular collapse. Despite intense investigation, the mechanism underlying the myocardial dysfunction of sepsis remains unclear. Macrophage migration inhibitory factor (MIF), an important cytokine released in sepsis and the acute respiratory distress syndrome, is a known cardiac depressant. We hypothesized that MIF released from the lung results in myocardial dysfunction during sepsis. In murine models of polymicrobial sepsis, we demonstrate a significant increase in the lungs of total and lavagable MIF between 20 and 30 h post induction of sepsis. At 30 h post sepsis, the lungs released MIF into the pulmonary circulation, increasing the plasma concentration by up to 51% in a single pass. Exogenous MIF, instilled into the lungs, increased alveolar keratinocyte-derived chemokine (KC), Macrophage inflammatory protein-2 (MIP2), and tumor necrosis factor alpha (TNFalpha) at 3 h, and plasma KC and MIP2 at 6 h postinstillation. This was associated with an increase in p38 mitogen-activated protein kinase and c-Jun N-terminal kinase phosphorylation. Because changes in mitogen-activated protein kinase activation can lead to myocardial depression, these data suggest that MIF released from the lungs may be responsible, at least in part, for the cardiac dysfunction seen in the late stages of sepsis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|