Accordingly, during homeostasis, the lung harbors at least one and perhaps two ontologically distinct populations of alveolar macrophages, referred to as tissue-resident alveolar macrophages (TR-AMs) and monocyte-derived alveolar macrophages (Mo-AMs).
In response to macrophage depletion, monocytes are recruited to the lung, where the microenvironment shapes them into cells that closely resemble tissue-resident alveolar macrophages ( Landsman and Jung, 2007 Hashimoto et al., 2013 Lavin et al., 2014 Gibbings et al., 2015). Van Furth and colleagues suggested an adult monocytic origin of all macrophages, but it is now clear that many tissue-resident macrophages, including alveolar macrophages in the lung, are self-renewing populations that arise from fetal progenitors and require minimal input from circuiting adult monocytes in a healthy environment ( Guilliams et al., 2013 Yona et al., 2013 Scott et al., 2014 Kopf et al., 2015 van de Laar et al., 2016). Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. Scott Budinger, Harris Perlman Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. Ridge, Neda Bagheri, Ali Shilatifard, G.R. Marshall, Ankit Bharat, Sergejs Berdnikovs, Sangeeta M. Morgan, Rana Saber, Alexander Shaffer, Monique Hinchcliff, Stacy A. Homan, Saul Soberanes, Salina Dominguez, Vince K. Gonzalez-Gonzalez, Khalilah Gates, Anna P. Yacoub, Monica Chi, Stephen Chiu, Francisco J. Williams, Hiam Abdala-Valencia, Tyrone J. McQuattie-Pimentel, Ching-I Chen, Kishore R. He also serves on the Arizona Trucking Association’s Board of Directors.Alexander V. Doughty serves on the Board of Directors and Executive Committee of Intelligent Transportation Society of America and as chair of its Governance Committee.
WILLIAM SUBLER NC PROFESSIONAL
He began his professional career at Discover Financial Services where he served in several executive positions over a 13-year period. and Quick Product Solutions, providers of nationwide transportation services as well as warehousing, packaging, and distribution. Doughty’s professional experience in transportation includes a decade as president of Moody’s Quick Inc.
Doughty served as the COO of Contractor Management Services for several years, where he helped lead the company’s growth through creative strategic and business planning, along with managing the introduction of service offerings for new vertical markets in the transportation sector. Prior to joining PrePass Safety Alliance in March 2013, Mr. Doughty is responsible for business planning, contracting and the day-to-day oversight of The Alliance’s service offerings. Mark Doughty serves as the President and Chief Executive Officer of PrePass Safety Alliance Mr.