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Plasma gelsolin enhances lung macrophage host defense against bacterial pneumonia in mice
Author(s) -
Yang Zhiping,
Chiou Terry,
Lee Po-Shun,
Stossel Tom,
Kobzik Lester
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.276.2
Subject(s) - gelsolin , microbiology and biotechnology , macrophage , bronchoalveolar lavage , inflammation , phagocytosis , lung , extracellular , alveolar macrophage , pneumonia , immunology , chemistry , biology , medicine , in vitro , biochemistry , actin
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 functions in the AM. rhu‐pGSN failed to enhance bacterial killing in NOS3−/− macrophages. pGSN binds sphingosine‐1‐phosphate (S1P), and may enhance its delivery to the S1P1 receptor. Both S1P and the S1P mimic, FTY720P, enhanced macrophage uptake and killing of bacteria, and activated macrophage NOS3 as well. Plasma gelsolin enhances innate resistance to pneumococcal pneumonia via lung macrophage NOS3, and is a potential immunomodulator for improving lung host defense against bacterial pneumonia. Support: NIH ES00002 ES11008