Immunohistochemical studies on gastrin-releasing peptide- and adrenocorticotropic hormone-containing cells in the human lung.

Bronchial endocrine cells containing gastrin-releasing peptide (GRP), a mammalian analog of bombesin, and adrenocorticotropic hormone (ACTH) were immunohistochemically localized in paraffin sections of normal and pathologic human lungs. GRP-containing cells were present in fetal bronchi at the 12th gestational week and in "neuroepithelial bodies" about the time of delivery. In normal adult lungs, a few isolated GRP-containing cells were present in bronchial and bronchiolar mucosa. In bronchiectatic or fibrotic lungs, small clusters of GRP-containing cells were occasionally noted in basal bronchial mucosa. Pronounced GRP cell hyperplasia often was observed in ectatic bronchioles of lungs with tumorlet. Cells of pulmonary tumorlets mostly showed GRP immunoreactivity. Two bronchial carcinoids exhibited a moderate number of GRP-containing cells. Three of four small cell carcinomas, intermediate cell type could be designated "GRPomas" from the number of GRP-containing cells present. In four of 11 small cell carcinomas, oat cell type, GRP immunoreactivity was infrequently recognized. Immunoabsorption tests indicated that GRP immunoreactivity in lungs would mainly fall under the C-terminal fragment rather than the whole sequence of GRP. Bombesin immunoreactivity in human lungs should be attributed to GRP or GRP-like molecules, since no bombesin immunoreactants were identified with bombesin antiserum which shows no cross-reactivity to porcine GRP. ACTH-containing cells, also reactive to beta-endorphin antiserum, were absent from normal fetal or adult lungs but did accompany GRP-containing cells occasionally in ectatic non-neoplastic bronchioles, always in tumorlet cells, and often in endocrine lung tumors, although the cells containing GRP and ACTH were not identical. The significance of GRP in the physiology and pathophysiology of the lung is discussed, and the necessity of reevaluation of "ectopic" ACTH production in lung neoplasms is proposed.