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

First Author  Immormino RM Year  2018
Journal  Am J Physiol Lung Cell Mol Physiol Volume  315
Issue  2 Pages  L202-L211
PubMed ID  29671604 Mgi Jnum  J:264363
Mgi Id  MGI:6193485 Doi  10.1152/ajplung.00067.2018
Citation  Immormino RM, et al. (2018) Neuropilin-2 regulates airway inflammatory responses to inhaled lipopolysaccharide. Am J Physiol Lung Cell Mol Physiol 315(2):L202-L211
abstractText  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-kappaB. 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.
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