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Immunomodulatory functions of the diffuse neuroendocrine system: Implications for bronchopulmonary dysplasia

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Abstract

Pulmonary neuroendocrine (NE) cells are believed to be the precursor of NE lung carcinomas, including well-differentiated (carcinoids) and moderately/poorly differentiated (atypical carcinoids and small-cell carcinomas, SCLCs) subtypes. In early studies, we determined mechanisms by which NE cell-derived peptides such as bombesin-like peptide (BLP) promote normal fetal lung development. Postnatally, BLP may normally regulate perinatal adaptation of the pulmonary circulation. However, elevated BLP levels in premature infants shortly after birth predict which infants are at high risk for developing bronchopulmonary dysplasia (BPD, chronic lung disease of newborns). An anti-BLP blocking antibody abrogates clinical and pathological evidence of lung injury in two baboon models of BPD. These observations indicate that BLP mediates lung injury in BPD, supporting a role for BLP as pro-inflammatory cytokines. We have directly tested the effects of BLP on eliciting inflammatory cell infiltrates in vivo. Surprisingly, mast cells are the major responding cell population. These data suggest that the diffuse NE system may be a newly recognized component of innate immunity in multiple organ systems. We speculate that overproduction of NE cell-derived peptides such as BLP may be responsible for a variety of chronic inflammatory disorders.

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Authors and Affiliations

  1. Departments of Pathology, Brigham & Women’s Hospital, Children’s Hospital, and Harvard Medical School, USA

    Mary E. Sunday MD, PhD, Lin Shan MD, PhD & Meera Subramaniam MD

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  1. Mary E. Sunday MD, PhD
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  2. Lin Shan MD, PhD
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  3. Meera Subramaniam MD
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Correspondence to Mary E. Sunday MD, PhD.

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This review is dedicated to the memory of Dr. Hugh Wolfe, one of the pioneers in the field of Endocrine Pathology. Hugh was much admired around the world as a leading scientist, an enthusiastic mentor, an ever-loyal friend, a cheerful neighbor, a beloved husband, and a proud father and grandfather. He died suddenly on September 6, 2001, and is greatly missed by all who knew him.

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Sunday, M.E., Shan, L. & Subramaniam, M. Immunomodulatory functions of the diffuse neuroendocrine system: Implications for bronchopulmonary dysplasia. Endocr Pathol 15, 91–106 (2004). https://doi.org/10.1385/EP:15:2:091

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