Plasma Gelsolin Enhances Lung Macrophage Host Defense Against Bacterial Pneumonia In Mice

Plasma gelsolin (pGSN) functions as part of the ‘extracellular actin scavenging system’ but its potential to improve host defense against infection has not been studied. Mice (C57BL/6, male) were pre-treated with recombinant human plasma gelsolin (rhu-pGSN, 400 mg/kg, s.c.) or vehicle 2 h before infection with Strep. pneumoniae (serotype 3, 150K CFU, i.n.) and evaluated 24 h later. rhu-pGSN caused enhanced bacterial clearance (% bacterial left alive in lungs, mean±SD: control, 88 ± 38 vs. rhu-pGSN-treated, 10 ± 5; n ≥ 13 mice/grp) and reduced acute inflammation (% BAL PMNs: control, 30 ± 11 vs. rhu-pGSN-treated, 8 ± 3). Similar results were seen with aerosolized rhu-pGSN. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria. rhu-pGSN caused an activating phosphorylation (ser1177) of macrophage nitric oxide synthase type III (NOS3), which has important bactericidal …