• Fengyong Yang, Jing Zhang, Yi Yang, Feng Ruan, Xinghua Chen, Junping Guo, Osama Abdel-Razek, Yi Y Zuo, and Guirong Wang.
• Department of Surgery, SUNY Upstate Medical University, Syracuse, New York.
• Shock. 2020 Oct 1; 54 (4): 507519507-519.

UnlabelledSurfactant protein B (SP-B) is essential for life and plays critical roles in host defense and lowering alveolar surface tension. A single-nucleotide polymorphism (SNP rs1130866) of human SP-B (hSP-B) alters the N-linked glycosylation, thus presumably affecting SP-B function. This study has investigated the regulatory roles of hSP-B genetic variants on lung injury in pneumonia-induced sepsis.MethodsWild-type (WT) FVB/NJ and humanized transgenic SP-B-T and SP-B-C mice (expressing either hSP-B C or T allele without mouse SP-B gene) were infected intratracheally with 50 μL (4 × 10 colony-forming units [CFUs]/mouse) Pseudomonas aeruginosa Xen5 or saline, and then killed 24 or 48 h after infection. Bacterial dynamic growths were monitored from 0 to 48 h postinfection by in vivo imaging. Histopathological, cellular, and molecular changes of lung tissues and bronchoalveolar lavage fluid (BALF) were analyzed. Surface tension of surfactants was determined with constrained drop surfactometry.ResultsSP-B-C mice showed higher bioluminescence and CFUs, increased inflammation and mortality, the higher score of lung injury, and reduced numbers of lamellar bodies in type II cells compared with SP-B-T or WT (P < 0.05). Minimum surface tension increased dramatically in infected mice (P < 0.01) with the order of SP-B-C > SP-B-T > WT. Levels of multiple cytokines in the lung of infected SP-B-C were higher than those of SP-B-T and WT (P < 0.01). Furthermore, compared with SP-B-T or WT, SP-B-C exhibited lower SP-B, higher NF-κB and NLRP3 inflammasome activation, and higher activated caspase-3.ConclusionshSP-B variants differentially regulate susceptibility through modulating the surface activity of surfactant, cell death, and inflammatory signaling in sepsis.

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