Fig. 8: Illustration of the impact of SPARCL1 on the progression of influenza pneumonia.

In influenza pneumonia, SPARCL1 from endothelial cells enters the alveoli via damaged blood vessels, prompting alveolar macrophages to adopt a pro-inflammatory (M1-like) state. This transformation hinges on SPARCL1 inducing TLR-4/NF-κB signaling activation in alveolar macrophages, leading to increased expression of pro-inflammatory cytokines. Simultaneously, heightened CCL-2 attracts more monocytes and macrophages into the alveoli. These recruited macrophages, once again exposed to SPARCL1 within the alveoli, further adopt a pro-inflammatory phenotype. The cumulative effect intensifies the local inflammatory response, causing tissue damage and hindering lung repair. Schematics and icons created with BioRender.com.