Chest
Translating Basic Research into Clinical PracticeAlternatively Activated Macrophages and Airway Disease
Section snippets
AAMs in Mouse Models of Lung Disease
One of the first lines of evidence that AAMs contribute to chronic inflammatory disease of any kind comes from a mouse model of chronic airway disease that develops after an infection with a common type of respiratory virus.4 In this model, infection with mouse parainfluenza virus or Sendai virus leads to acute bronchiolitis followed by chronic airway disease that appears to mimic the sequence of events found in childhood asthma after infection with closely related human pathogens, such as
AAMs in Human Lung Disease
Macrophages are implicated in the development of airway inflammation and mucus production as well as the alveolar destruction that are all characteristic of COPD. Studies of mouse models and humans with COPD support a role for M1 macrophages in alveolar destruction as a basis for pulmonary emphysema.25 One study indicated that the pattern of gene expression in alveolar macrophages from smokers showed at least some overlap with genes found in mouse models of COPD, and this overlap included genes
AAM Biomarkers in Airway Disease
To the extent that AAMs drive chronic airway disease, they also offer an opportunity to monitor and stratify patients and thereby personalize diagnosis and treatment. Toward that end, an effort is being made to compile markers of AAM levels and/or activity that could be validated in experimental models and applied to patients with chronic obstructive lung disease. Two major challenges in this approach are the difficulties in predicting human orthologs of mouse genes and verifying that either
Future Directions
In this brief review, we highlight evidence that AAMs contribute to the pathogenesis of chronic airway diseases. This disease mechanism is supported by evidence from experimental models of postviral airway disease and translational studies of asthma and COPD in humans. In both cases, ongoing work needs to further define the basis for AAM activation as a means to better understand pathogenesis. Even at this stage of understanding, investigators have begun to develop clinical biomarkers of AAM
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Holtzman is the principal investigator of research grants from the National Institutes of Health, Hoffmann-La Roche Inc, and Forest Institute Inc to Washington University and has received honorariums for talks at other universities from Merck. Dr Byers has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed
References (48)
- et al.
Alternative activation of macrophages: mechanism and functions
Immunity
(2010) - et al.
Immune pathways for translating viral infection into chronic airway disease
Adv Immunol
(2009) - et al.
Expression of the Ym2 lectin-binding protein is dependent on interleukin (IL)-4 and IL-13 signal transduction: identification of a novel allergy-associated protein
J Biol Chem
(2001) - et al.
Recent advances in the pathophysiology of asthma
Chest
(2010) - et al.
Obligatory role for interleukin-13 in obstructive lesion development in airway allografts
Am J Pathol
(2006) - et al.
Characterization of macrophage activation states in patients with cystic fibrosis
J Cyst Fibros
(2010) - et al.
Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis
Respir Med
(2010) - et al.
Exploring the full spectrum of macrophage activation
Nat Rev Immunol
(2008) - et al.
Alternative activation of macrophages: an immunologic functional perspective
Annu Rev Immunol
(2009) - et al.
Interleukin 12 p40 production by barrier epithelial cells during airway inflammation
J Exp Med
(2001)
Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease
Nat Med
Macrophages: regulators of sex differences in asthma?
Am J Respir Cell Mol Biol
Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia
J Exp Med
New immune pathways from chronic post-viral lung disease
Ann N Y Acad Sci
Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis
J Clin Invest
Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation
Science
Interleukin-13-dependent expression of matrix metalloproteinase-12 is required for the development of airway eosinophilia in mice
Am J Respir Cell Mol Biol
Alternatively activated macrophages as cause or effect in airway disease
Am J Respir Cell Mol Biol
Female mice are more susceptible to the development of allergic airway inflammation than male mice
Clin Exp Allergy
Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites
Nat Med
Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection
J Immunol
Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production
Science
IL-13 production by NK cells: IL-13-producing NK and T cells are present in vivo in the absence of IFN-gamma
J Immunol
Human eosinophils express and release IL-13 following CD28-dependent activation
J Leukoc Biol
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Funding/Support: The research reviewed here was supported by grants from the National Institutes of Health (National Heart, Lung, and Blood Institute and National Institute of Allergy and Infectious Diseases) and the Martin Schaeffer Fund.
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