High levels of PGE2 in bone marrow transplant mice impairs autophagy in alveolar macrophages

• Published in: The Journal of immunology (1950) 2016-05, Vol.196 (1_Supplement), p.60-60.26
• Main Authors: Martinez-Colon, Giovanny Joel, Moore, Bethany B
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.60.26

Bone marrow transplantation (BMT) is commonly used as a therapeutic strategy to treat different health disorders such as cancer. Although it benefits the host by restoring a damaged immune system with a healthy immune system, BMT recipients develop different complications in handling pulmonary pathogens. Previous studies have shown that immune and structural cells in the lungs of BMT recipients highly express cyclooxygenase (COX)-2, leading to overproduction of immunosuppressive prostaglandin E2 (PGE2) and may explain the susceptibility observed in BMT recipients to opportunistic pathogens such as Pseudomonas aeruginosa. Alveolar macrophages reside in the lower airways where they compose the first line of host defense against a wide array of pathogens. Previous studies have demonstrated that alveolar macrophages can target and clear pathogens such as Pseudomonas aeruginosa via autophagy, a mechanism by which pathogens are encapsulated in an autophagosome wherein the bacterial components are targeted for degradation. We have evidence that BMT recipient mouse alveolar macrophages harbor a deficiency in autophagy. To determine if PGE2 regulates autophagy in alveolar macrophages, we performed a series of in vitro and in vivo assays using a syngeneic BMT mouse model. Our results indicate impaired autophagy activity in alveolar macrophages in the presence of exogenous PGE2 as well as in the lung compartment of BMT mice. These observations highlight targeting the PGE2 signaling pathway as a method to restore immune activity in alveolar macrophages post-BMT.