Abstract 1883 Neonatal Pulmonology II: Oxidant and Inflammatory Lung Injury Poster Symposium, Tuesday, 5/4

Hyaluronan (HA), a glycosaminoglycan polymer of N-acetyl glucosamine and glucuronic acid, has been implicated in inflammatory responses including monocyte activation, chemotaxis and cytokine gene expression. We have developed an HA-binding peptide (HABP) that inhibits chemotaxis of U937 cells by 60% in vitro. In the current studies, we used the bleomycin model of lung injury to examine the role of HA in vivo. We administered intratracheal (IT) bleomycin (8U/kg) or an equivalent volume of saline to rats, with untreated animals as controls. Respiratory rates were used to quantify respiratory distress and glucosaminidase activity (Gluc Act) of lavage cells were used as a measure of inflammation. Serum [HA] was determined using a radiometric kit. Surfactant function was assessed by minimum surface tension (ST) of lavage using a bubble surfactometer and by determination of deflation stability using pressure-volume curves. At 7 days, IT bleomycin animals ± HABP or scrambled peptide (each 80 mg/kg SQ) were compared to saline-treated and untreated rats. Results are mean ± sem; n≥5/group; *p < 0.05 compared to both bleomycin alone and bleomycin + scrambled peptide groups (ANOVA): (Table)

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Rats given IT bleomycin ± Scrambled Peptide showed decreased deflation stability as compared to untreated or IT saline-treated animals. Injured rats given HABP had deflation stability similar to that of controls. Phospholipid content/composition was similar in all groups. SP-A mRNA was unaffected, and SP-B/SP-C mRNAs were decreased to 40%/30% in injured rats. By immunohistochemistry of lung sections from IT bleomycin ± Scrambled Peptide, SP-B/C staining was absent in injured areas of the lung whereas SP-A staining was normal. Lung histology and SP-B/C staining of injured animals given HABP were similar to uninjured controls. We conclude that elevated HA is likely a critical component in the response to acute lung injury and that HABP prevents surfactant deficiency after injury, in part by maintaining SP-B/C gene expression. We speculate that HABP may be a useful preventative therapy for the response to acute lung injury.

Funded by March of Dimes, ALA and NIH HL56401