Abstract Introduction HIV-associated lung injury features oxidative stress, inflammation, and mitochondrial dysfunction, including Tat-driven disruption of mitochondrial homeostasis activity. People living with HIV (PLWH) smoke tobacco products, and HIV is an independent factor for lung abnormalities. Tobacco smoke may augment HIV lung pathogenesis. To directly model HIV protein effects in the lung, we use SPC-Tat (SPC-surfactant producing epithelial cells) transgenic mice (lung epithelial Tat expression) combined with cigarette smoke (CS) exposure to determine the role of HIV Tat in CS-induced pathogenesis of obstructive lung disease in PLWH. Methods Two-month-old SPC-Tat transgenic mice and FVB wild-type controls were housed under standard laboratory conditions in the University of Rochester vivarium. CS exposure was performed using a CH Tech Baumgartner smoking machine (3R4F research-grade cigarettes per run) for 2-hour sessions with a 1-hour interval, 5 days per week for 3 months, maintaining 200-250 mg/m³ total particulate matter (TPM). Each group (SPC-AIR, SPC-CS, FVB-AIR, and FVB-CS) included a minimum of six mice. At the end of each month, one male and one female mouse were euthanized to assess airspace enlargement/obstructive lung changes. Lungs were isolated, and the largest lobe was inflated with low-melting agarose prior to paraffin embedding. H&E staining was performed, and alveolar structural changes were evaluated microscopically at 20X. KC and MCP-1, ELISA were also conducted on theses lung tissue homogenate. Results After one month of CS exposure, no significant alterations in alveolar architecture were observed in either FVB or SPC-TAT mice compared with their respective air controls. However, two months of continuous CS exposure induced a marked increase in alveolar macrophage infiltration, indicating an active inflammatory response. This finding was further supported by elevated levels of KC and MCP-1 detected in the CS-exposed groups. Mild alveolar wall disruption and early airspace enlargement were also evident, though the extent of structural damage remained below that observed in fully developed emphysematous lungs. Conclusion CS exposure caused progressive lung injury characterized by inflammation and early alveolar damage in SPC-Tat mice. Tat expression in surfactant secreting epithelial cells exhibited an enhanced inflammatory response. Further studies are ongoing to determine the effect of chronic CS exposure in airspace enlargement associated with lung obstructive/restrictive changes along with lung remodeling in SPC-Tat mice, with an intent to ameliorate the effects by novel biologics and pharmacological agents. This abstract is funded by: National Institutes of Health
Faizan et al. (Fri,) studied this question.