Inhibitory effects of collismycin C and pyrisulfoxin A on particulate matter-induced pulmonary injury

Background: Inhalation of fine particulate matter (PM_2.5)is associated with elevated pulmonary injury caused by the loss of vascular barrier integrity. Marine microbial natural products isolated from microbial culture broths were screened for pulmonary protective effects against PM_2.5. Two 2,2′-bipyridine compounds isolated from a red alga-associated Streptomyces sp. MC025—collismycin C (2)and pyrisulfoxin A (5)—were found to inhibit PM_2.5-mediated vascular barrier disruption. Purpose: To confirm the inhibitory effects of collismycin C and pyrisulfoxin A on PM_2.5-induced pulmonary injury Study design: In this study, we investigated the beneficial effects of collismycin C and pyrisulfoxin A on PM-induced lung endothelial cell (EC)barrier disruption and pulmonary inflammation. Methods: Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS)generation, and histology were evaluated in PM_2.5-treated ECs and mice. Results: Collismycin C and pyrisulfoxin A significantly scavenged PM_2.5-induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase as well as activated Akt, which helped in maintaining endothelial integrity, in purified pulmonary endothelial cells. Furthermore, collismycin C and pyrisulfoxin A reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid of PM-treated mice. Conclusion: These data suggested that collismycin C and pyrisulfoxin A might exert protective effects on PM-induced inflammatory lung injury and vascular hyperpermeability.