PMID- 37994278 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20240201 IS - 2051-817X (Electronic) IS - 2051-817X (Linking) VI - 11 IP - 22 DP - 2023 Nov TI - Neuropeptide stimulation of physiological and immunological responses in precision-cut lung slices. PG - e15873 LID - 10.14814/phy2.15873 [doi] LID - e15873 AB - Organotypic lung slices, sometimes known as precision-cut lung slices (PCLS), provide an environment in which numerous cell types and interactions can be maintained outside the body (ex vivo). PCLS were maintained ex vivo for up to a week and demonstrated health via the presence of neurons, maintenance of tissue morphology, synthesis of mucopolysaccharides, and minimal cell death. Multiple phenotypes of neuronal fibers were present in lung slices with varied size, caliber, and neurotransmitter immunoreactivity. Of the neuropeptides present in fibers, calcitonin gene-related peptide (CGRP) was the most prevalent. Exposing PCLS to recombinant CGRP resulted in the proliferation and dispersion of CD19(+) B cells in slices taken selectively from females. The number of granules containing immunoreactive (ir) surfactant protein C (SPC), which are representative of alveolar type 2 cells, increased in slices from females within 24 h of exposure to CGRP. Additionally, ir-SPC granule size increased in slices from males and females across 48 h of exposure to CGRP. Exposure of PCLS to exogenous CGRP did not alter the number of solitary pulmonary neuroendocrine cells (PNEC) but did result in neuroendocrine bodies that had significantly more cells. Neuronal fiber numbers were unchanged based on ir-peripherin; however, ir-CGRP became non-detectable in fibers while unchanged in PNECs. The effects of exogenous CGRP provide insight into innate immune and neuroendocrine responses in the lungs that may be partially regulated by neural fibers. The sex-dependent nature of these changes may point to the basis for sex-selective outcomes among respiratory diseases. CI - (c) 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. FAU - Patlin, B AU - Patlin B AD - Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado, USA. FAU - Schwerdtfeger, L AU - Schwerdtfeger L AD - Department of Neurology, Harvard Medical School and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Tobet, S AU - Tobet S AUID- ORCID: 0000-0002-1615-7331 AD - School of Biomedical Engineering and Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA. LA - eng GR - U54 MH118919/MH/NIMH NIH HHS/United States GR - U54-MH118919/GF/NIH HHS/United States PT - Journal Article PL - United States TA - Physiol Rep JT - Physiological reports JID - 101607800 RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) RN - 0 (Neuropeptides) SB - IM MH - Male MH - Female MH - Humans MH - *Calcitonin Gene-Related Peptide/pharmacology/metabolism MH - *Neuropeptides/pharmacology/metabolism MH - Lung/metabolism MH - Neurons/metabolism MH - Thorax PMC - PMC10665790 OTO - NOTNLM OT - calcitonin gene-related peptide OT - neural fibers OT - precision-cut lung slice OT - pulmonary neuroendocrine cells OT - surfactant COIS- No conflicts of interest, financial or otherwise, are declared by the authors. EDAT- 2023/11/23 06:42 MHDA- 2023/11/27 12:43 PMCR- 2023/11/23 CRDT- 2023/11/23 04:06 PHST- 2023/11/01 00:00 [revised] PHST- 2023/06/14 00:00 [received] PHST- 2023/11/04 00:00 [accepted] PHST- 2023/11/27 12:43 [medline] PHST- 2023/11/23 06:42 [pubmed] PHST- 2023/11/23 04:06 [entrez] PHST- 2023/11/23 00:00 [pmc-release] AID - PHY215873 [pii] AID - 10.14814/phy2.15873 [doi] PST - ppublish SO - Physiol Rep. 2023 Nov;11(22):e15873. doi: 10.14814/phy2.15873.