Mice With Targeted Deletion of Receptor for Hyaluronan‐Mediated Motility (RHAMM, CD168) Are Protected From Bleomycin‐Induced Lung Injury

Abstract

Acute lung injury results in inflammation, Surfactant Protein B (SPB) deficiency and respiratory distress. Hyaluronan (HA) and its receptor RHAMM have been implicated in the inflammatory response to lung injury. We hypothesized that RHAMM KO mice would be protected from bleomycin‐induced lung injury. Littermate wild type (WT) and RHAMM KO mice were treated with IT 1U/kg bleomycin in 25μl saline or with 25μl saline alone. IT bleomycin in WT controls resulted in decreased body weight, and increased respiratory rate by d7‐10. RHAMM KO mice given IT bleomycin had significantly less weight loss and respiratory distress than WT mice. Compared to injured WT animals, RHAMM KO mice had lower lavage concentrations of HA, as well as lower neutrophil and macrophage enzyme activities. In injured WT mice on d7, western blot for SPB showed decreased expression of the mature 16‐kDa dimer, but no change in SPB expression was seen in injured RHAMM KO mice. We conclude that RHAMM KO mice have less inflammation, SPB deficiency and respiratory distress after acute lung injury. We speculate that these data are important for future development of novel therapeutic approaches to limit the severity of lung disease.