Macrophage migration inhibitory factor is a novel determinant of cigarette smoke-induced lung damage

Jonathan Fallica, Laurent Boyer, Bo Kim, Leonid Serebreni, Lidenys Varela, Omar Hamdan, Lan Wang, Tiffany Simms, Mahendra Damarla, Todd M Kolb, Richard Bucala, Wayne Mitzner, Paul M Hassoun, Rachel Damico
American Journal of Respiratory Cell and Molecular Biology 2014, 51 (1): 94-103
Cigarette smoke (CS) is the most common cause of chronic obstructive pulmonary diseases (COPD), including emphysema. CS exposure impacts all cell types within the airways and lung parenchyma, causing alveolar tissue destruction through four mechanisms: (1) oxidative stress; (2) inflammation; (3) protease-induced degradation of the extracellular matrix; and (4) enhanced alveolar epithelial and endothelial cell (EC) apoptosis. Studies in human pulmonary ECs demonstrate that macrophage migration inhibitory factor (MIF) antagonizes CS-induced apoptosis. Here, we used human microvascular ECs, an animal model of emphysema (mice challenged with chronic CS), and patient serum samples to address both the capacity of CS to alter MIF expression and the effects of MIF on disease severity. We demonstrate significantly reduced serum MIF levels in patients with COPD. In the murine model, chronic CS exposure resulted in decreased MIF mRNA and protein expression in the intact lung. MIF deficiency (Mif(-/-)) potentiated the toxicity of CS exposure in vivo via increased apoptosis of ECs, resulting in enhanced CS-induced tissue remodeling. This was linked to MIF's capacity to protect against double-stranded DNA damage and suppress p53 expression. Taken together, MIF appears to antagonize CS-induced toxicity in the lung and resultant emphysematous tissue remodeling by suppressing EC DNA damage and controlling p53-mediated apoptosis, highlighting a critical role of MIF in EC homeostasis within the lung.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"