Figure 4

Gene expression of components of the kinin–kallikrein system point to alveolar cells role. (a) Schematic representing the main players and steps of the bradykinin system, also known as the kinin–kallikrein system. High molecular weight kininogen (KNG1) conversion into bradykinin is catalyzed by kallikrein. Bradykinin binds to the bradykinin receptor 2 (BDKRB2), but it can be converted into DR9-bradykinin, which activates the bradykinin receptor 1 (BDKRB1) until it is degraded by ACE2 into inactive degradation products. Bradykinin can also be directly converted into inactive degradation products by ACE. 1–6 Visualization of gene expression in dbMAP embeddings of the lung atlas. 1 KNG1 is selectively expressed in alveolar cells. 2 KLKB1 is expressed in endothelial and lymph vessel cells, and sparsely expressed in alveolar cells. 3 BDKRB2 expression is selective to endothelial cells. 4 ACE expression is selective to endothelial cells and macrophages. 5 BDKRB1 expression is selective to endothelial cells and fibroblasts, but also detected in low levels in alveolar cells. 6 ACE2 expression is restricted to alveolar cells. (b) Dot plot visualization of expression of genes involved in the bradykinin system in the lung atlas cell types. ACE2 and KNG1 gene expression is selective to alveolar clusters, despite ACE2 being lowly expressed in a large portion of endothelial cells and KNG1 also being lowly expressed in a large portion of clusters of macrophages. KLKB1 is highly expressed in endothelial and lymph vessel cells, but also lowly expressed in T CD4 clusters. BDKRB2 is highly expressed in endothelial and alveolar type 1.1 cells, and also less expressed by a large portion of B/plasma cells, and of macrophages clusters 7 and 8. ACE is selectively expressed in endothelial cells and in macrophages. BDKRB1 expression is selective to fibroblasts, although various clusters express it in low levels. ACE2 expression is restricted to alveolar cells.