Dead cells present a rich “meal” of proteins, lipids, and carbohydrates to engulfing macrophages. We have characterized the response of macrophages to engulfment of live, apoptotic, or necrotic cells and identified accumulation of polyamines as a unique response to engulfment of apoptotic cells (a process termed efferocytosis). We have found that polyamine accumulation is required for part of efferocytosis-induced immunomodulation and seek to understand this mechanism. Funded by NHLBI R00 HL141658 (McCubbrey PI).
Dead cells are known to promote lung repair in vivo, and prior work has attributed this to macrophage-apoptotic cell interactions that change macrophage function. However, many other phagocytes are present in the lung and tissue damage generates many types of dead cells, collectively termed cell corpses. We are currently studying how interactions with cell corpses broadly promote fibroblast pro-repair function through a metabolite-dependent mechanism that regulates proliferation and collagen synthesis.
Macrophages exist in distinct tissue compartment of the lung, most superficially in the airspace (alveolar macrophages) or the lung tissue (interstitial macrophages). Tissue resident macrophages self-renew at these sites throughout life, but additional monocyte-derived macrophages are recruited in response to lung injury. Through lineage-tracing, single cell sequencing, and tissue section stereology we seek to understand these macrophage subsets and their functions during homeostasis, injury, and repair. Funded by NHLBI R01 HL149741 (McCubbrey Co-I).