Neuraminidase Reprograms Lung Tissue and Potentiates Lipopolysaccharide-Induced Acute Lung Injury in Mice

Abstract

We previously reported that removal of sialyl residues primed PBMCs to respond to bacterial LPS stimulation in vitro. Therefore, we speculated that prior desialylation can sensitize the host to generate an enhanced inflammatory response upon exposure to a TLR ligand, such as LPS, in a murine model of acute lung injury. Intratracheal instillation of neuraminidase (NA) 30 min prior to intratracheal administration of LPS increased PMNs in the bronchoalveolar lavage fluid (BALF) and the wet-to-dry lung weight ratio, a measure of pulmonary edema, compared to mice that received LPS alone. Administration of NA alone resulted in desialylation of bronchiolar and alveolar surfaces and induction of TNF-α, IL-1β, and chemokines in lung homogenates and BALF; however, PMN recruitment in mice treated with NA alone did not differ from those of PBS-administered controls. NA pretreatment alone induced apoptosis and markedly enhanced LPS-induced endothelial apoptosis. Administration of recombinant Bcl-2, an anti-apoptotic molecule, abolished the effect of NA treatment on LPS-induced PMN recruitment and pulmonary edema formation. We conclude that NA pretreatment potentiates LPS-induced lung injury through enhanced PMN recruitment, pulmonary edema formation, and endothelial and myeloid cell apoptosis. A similar “reprogramming” of immune responses with desialylation may occur during respiratory infection with NA-expressing microbes and contribute to severe lung injury.

Metabolic sialic acid blockade lowers the activation threshold of moDCs for TLR stimulation

“…Several groups have reported that removal of surface sialic acids with bacterial sialidases enhanced the response of DCs to LPS. In addition to enhanced maturation and cytokine production upon LPS stimulation, DCs treated with sialidase were also more potent T‐cell activators 8 , 9 , 10 , 11 , 12 , 13 , 14 . These data evidence that sialic acids limit the response of DCs to stimulation via the TLR pathway.…”

Novel strategies for targeting innate immune responses to influenza

“…Lung tissue was then air dried for 5-6 days and re-weighed everyday until a dry weight was stable and this acted as the final dry weight. The W/D weight ratio was calculated by dividing the wet by the final dry weight 59 .…”

Galectin CvGal2 from the Eastern Oyster (Crassostrea virginica) Displays Unique Specificity for ABH Blood Group Oligosaccharides and Differentially Recognizes Sympatric Perkinsus Species

“…The dissected tissues, pallial fluid cell pellet, and hemocytes freshly isolated as described above were lysed by sonication in PBS containing protease inhibitors cocktail (Calbiochem), and the clear supernatant was collected after centrifugation at 3000 rpm for 10 min at 4 °C. For isolation of total RNA the freshly isolated hemocytes, pallial fluid cell pellet, and the aforementioned tissues were extracted by using TRIzole reagent (Invitrogen) as previously described (36). RNA was quantified in a Nanodrop Bioanalyzer at 260/280 nm.…”