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Excess neuropeptides in lung signal through endothelial cells to impair gas exchange

Jinhao Xu1, Le Xu2, Pengfei Sui3

  • 1Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.

Developmental Cell
|March 18, 2022
PubMed

Insights

Excess neuropeptides from pulmonary neuroendocrine cells (PNECs) cause respiratory distress and hypoxemia in infants. Blocking these neuropeptides, like calcitonin gene-related peptide (CGRP), can reduce lung fluid and improve gas exchange.

Area of Science:

  • Pulmonary Medicine
  • Endocrinology
  • Cell Biology

Background:

  • Increased neuropeptides are observed in respiratory distress but their role is unclear.
  • Neuroendocrine cell hyperplasia of infancy involves elevated pulmonary neuroendocrine cells (PNECs).

Purpose of the Study:

  • To investigate the role of PNEC-derived neuropeptides in infant respiratory distress.
  • To determine if neuropeptides contribute to hypoxemia and lung fluid accumulation.

Main Methods:

  • Utilized a mouse model of neuroendocrine cell hyperplasia of infancy.
  • Examined the effects of elevated calcitonin gene-related peptide (CGRP) on endothelial cells.
  • Assessed interventions including PNEC prevention, CGRP gene inactivation, and CGRP receptor antagonism.

Main Results:

  • Excess PNEC-derived neuropeptides, particularly CGRP, activate endothelial receptors, increasing lung permeability and fluid, leading to hypoxemia.
  • Preventing PNEC formation or blocking CGRP signaling ameliorated lung fluid and hypoxemia.
  • Elevated neuropeptides were also found in human acute respiratory distress syndrome.

Conclusions:

  • PNEC-derived neuropeptides are a key driver of pulmonary complications in infant respiratory distress.
  • Targeting neuropeptide function, specifically CGRP, offers a potential therapeutic strategy for lung fluid and gas exchange improvement.

Keywords:
lung functionneuropeptidespediatric diseasepulmonary neuroendocrine cells

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