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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Neuropilin-2 regulates airway inflammatory responses to inhaled lipopolysaccharide.

Authors: Immormino, Robert M; Lauzier, David C; Nakano, Hideki; Hernandez, Michelle L; Alexis, Neil E; Ghio, Andrew J; Tilley, Stephen L; Doerschuk, Claire M; Peden, David B; Cook, Donald N; Moran, Timothy P

Published In Am J Physiol Lung Cell Mol Physiol, (2018 Aug 01)

Abstract: Neuropilins are multifunctional receptors that play important roles in immune regulation. Neuropilin-2 (NRP2) is expressed in the lungs, but whether it regulates airway immune responses is unknown. Here, we report that Nrp2 is weakly expressed by alveolar macrophages (AMs) in the steady state but is dramatically upregulated following in vivo lipopolysaccharide (LPS) inhalation. Ex vivo treatment of human AMs with LPS also increased NRP2 mRNA expression and cell-surface display of NRP2 protein. LPS-induced Nrp2 expression in AMs was dependent upon the myeloid differentiation primary response 88 signaling pathway and the transcription factor NF-κB. In addition to upregulating display of NRP2 on the cell membrane, inhaled LPS also triggered AMs to release soluble NRP2 into the airways. Finally, myeloid-specific ablation of NRP2 resulted in increased expression of the chemokine (C-C motif) ligand 2 ( Ccl2) in the lungs and prolonged leukocyte infiltration in the airways following LPS inhalation. These findings suggest that NRP2 expression by AMs regulates LPS-induced inflammatory cell recruitment to the airways and reveal a novel role for NRP2 during innate immune responses in the lungs.

PubMed ID: 29671604 Exiting the NIEHS site

MeSH Terms: Administration, Inhalation; Animals; Chemokine CCL2/genetics; Chemokine CCL2/immunology; Immunity, Innate/drug effects*; Immunity, Innate/genetics; Lipopolysaccharides/toxicity*; Lung/immunology*; Lung/pathology; Macrophages, Alveolar/immunology*; Macrophages, Alveolar/pathology; Mice; Mice, Knockout; Neuropilin-2/genetics; Neuropilin-2/immunology*; Signal Transduction/drug effects*; Signal Transduction/genetics; Signal Transduction/immunology; Up-Regulation/drug effects*; Up-Regulation/immunology

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