Fig. 5.

Delayed, pharmacological augmentation of air space heparan sulfate (HS) degradation activity worsens bleomycin (Bleo)-induced lung injury. A: to augment air space HS degradation (i.e., heparanase) activity, a mixture of bacterial heparinase I/III (HepI/III; at a dose designed to avoid disruption of alveolar barrier function in control mice) was administered (via bilateral intrabronchial injection) 10 and 16 days after intratracheal bleomycin (or saline). Intrabronchial heat-inactivated (HI) heparinase I/III was administered as a control. B: active heparinase I/III induced mortality in bleomycin-treated mice (log-rank test), which met the moribund criteria as determined by a blinded observer. C–F: before euthanasia, heparinase I/III-treated mice demonstrated increased bronchoalveolar lavage (BAL) protein (C), decreased pulmonary function (D and E), and increased lung inflammation (F). Heat-inactivated heparinase I/III had no effect on either saline- or bleomycin-treated mice. One-way ANOVA with Holm-Sidak testing was used for multiple comparisons. *P < 0.05. Error bars represent SE.