Pulmonary Macrophages: A New Therapeutic Pathway in Fibrosing Lung Disease?

Trends

In the healthy lung, at least two macrophage populations exist, alveolar macrophages (AMs) and interstitial macrophages (IMs), which may be distinguished by their unique combination of surface markers. A third population of monocyte-derived macrophages (MDMs) may be recruited during inflammatory responses.

Lung-resident macrophages are long-lived cells derived from embryonic precursors which replenish their populations by self-renewal under homeostatic conditions.

It is becoming increasingly apparent that the M1/M2 paradigm lacks usefulness when considering disease states in the lung. In fact, macrophages often co-express markers of M1/M2 activation, indicating that these cells are highly plastic and may represent a sliding scale of activation states rather than being terminally differentiated distinct lineages.

Multiple macrophage-derived phenotypic markers, cytokines, and products have been suggested as possible targets for intervention in fibrotic lung disease.

Pulmonary fibrosis (PF) is a growing clinical problem which can result in breathlessness or respiratory failure and has an average life expectancy of 3 years from diagnosis. Therapeutic options for PF are limited and there is therefore a significant unmet clinical need. The recent resurgent interest in macrophage biology has led to a new understanding of lung macrophage origins, biology, and phenotypes. In this review we discuss fibrotic mechanisms and focus on the role of macrophages during fibrotic lung disease. Data from both human and murine studies are reviewed, highlighting novel macrophage-orientated biomarkers for disease diagnosis and potential targets for future anti-fibrotic therapies.