Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease
Maor Sauler1, Lin Leng, Mark Trentalange
1Section of Pulmonary, Critical Care, and Sleep Medicine, Yale Univ. School of Medicine, PO Box 208057, 300 Cedar St., New Haven, CT 06520-8057. patty.lee@yale.edu.
Summary
Macrophage migration inhibitory factor (MIF) and its receptor CD74 are crucial for maintaining lung structure. Lower MIF levels are linked to chronic obstructive pulmonary disease (COPD) development and severity.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- The mechanisms driving chronic obstructive pulmonary disease (COPD) pathogenesis are not fully understood.
- Cellular senescence and apoptosis are implicated in COPD development, but key regulators are unknown.
- Macrophage migration inhibitory factor (MIF) antagonizes apoptosis and senescence, suggesting a potential role in COPD.
Purpose of the Study:
- To investigate the role of Macrophage Migration Inhibitory Factor (MIF) and its receptor CD74 in the pathogenesis of chronic obstructive pulmonary disease (COPD).
Main Methods:
- Mice lacking MIF (Mif(-/-)) or CD74 (Cd74(-/-)) and wild-type (WT) controls were aged for 6 months.
- Mice were exposed to cigarette smoke to assess susceptibility to COPD.
- Plasma MIF concentrations were measured in a cohort of 224 human participants, including a subgroup of smokers with and without COPD.
Main Results:
- Mice deficient in MIF or CD74 developed spontaneous emphysema, increased lung volume, and elevated senescence markers (p53/21, p16).
- Mif(-/-) mice exhibited increased susceptibility to cigarette smoke-induced COPD and apoptosis.
- Human subjects with COPD had significantly lower plasma MIF concentrations compared to those without COPD.
Conclusions:
- MIF and its receptor CD74 are essential for maintaining normal alveolar structure in mice.
- Reduced MIF levels are associated with the presence and severity of COPD in human smokers.
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