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Allele-specific SF-A2 binding may aid understanding of lung disease

The protective role of surfactant protein-A in limiting mycoplasma membrane fraction-stimulated protein production may aid our understanding of how these proteins affect lung disease, according to recent research.

“To our knowledge, our findings show for the first time that genetic alteration in 1 aa of hSP-A2 at position Q223K (1A⁰ versus 1A³) can dramatically impair SP-A2 from binding the pathogen [mycoplasma membrane fractions (MMF)], which consequently leads to a heightened innate response that was not significantly different from when SP-A is absent altogether,” Julie G. Ledford, PhD, of the department of medicine at Duke University Medical Center, and colleagues wrote. “These findings highlight the importance of functional [surfactant protein-A (SP-A)] in the host response and provide new insight into the functional role of genetic variation of hSP-A in airways disease.”

The researchers previously identified SP-A as binding easily to Mycoplasma pneumoniae and mycoplasma membrane fractions, but also to non-infectious membranes from M. pneumoniae as well as limiting epidermal growth factor receptor (EGFR) signaling. Ledford and colleagues concluded this SP-A and EGFR interaction was allele specific.

“Novel humanized SP-A2–transgenic mice harboring the hSP-A2 223K allele exhibit reduced neutrophil influx and mucin production in the lungs when challenged with MMF compared with SP-A2/2 mice,” Ledford and colleagues wrote. “Conversely, mice expressing hSP-A2 223Q have increased neutrophil influx and mucin production that are similar to SP-A–null mice. Using tracheal epithelial cell cultures, we show that enhanced mucin production to MMF occurs in the absence of SP-A and is not dependent upon neutrophil recruitment.”

Researchers also found increased EGFR phosphorylation in mice where SP-A was absent, indicating it is not neutrophil recruitment dependent. Additionally, they were able to reduced mucin production in MMF–challenged SP-A–null mice.

“Taken together, these finding suggest that when SP-A is absent (as in SP-A–null mice) or has a lower binding affinity for MMF (as in SPA223Q/2 mice), MMF will cause increased p-EGFR signaling that results in enhanced mucin production,” Ledford and colleagues wrote. – by Jeff Craven

Disclosure: The researchers report no relevant financial disclosures.