Comparison of the ontogeny of protein gene product 9.5, chromogranin A and proliferating cell nuclear antigen in developing human lung.
Pulmonary neuroendocrine cell products, especially bombesin-like peptides, are important modulators of fetal lung growth, morphogenesis and maturation. In the present study, we describe the ontogeny of protein gene product 9.5 (PGP 9.5) in 28 midtrimester human fetal lungs, in comparison to chromogranin A (CGA), a marker of differentiated neuroendocrine cells, and proliferating cell nuclear antigen (PCNA), which is expressed by actively dividing cells. PGP 9.5 immunostaining colocalized with CGA in many cells, although the peak abundance of PGP 9.5 preceded that of CGA by 4 to 6 weeks. In addition, a novel staining pattern was noted for PGP 9.5: diffuse cytoplasmic staining of undifferentiated epithelial cells, which was demonstrated by all of the airways before 15 weeks gestation. After gestational week 15, only the smallest airways demonstrated this pattern. PCNA immunostaining demonstrated age-dependent regional variation. All samples had approximately 25% epithelial cells immunopositive for PCNA. Between 11 and 14 weeks gestation over 50% of the mesenchymal cells were PCNA positive. This mesenchymal staining decreased after 14 weeks, and was rare by week 19. There was no definite correlation between the immunostaining for PGP 9.5 and that for PCNA, although PGP 9.5 positive cells were usually PCNA negative. These observations suggest that other growth factors produced by non-neuroendocrine epithelial cells also participate in lung development.
Haley
K J
KJ
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Drazen
J M
JM
Osathanondh
R
R
Sunday
M E
ME
D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry* / Q000196:embryology*; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D013869:Thiolester Hydrolases / Q000032:analysis*; D043222:Ubiquitin Thiolesterase
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D018809:Proliferating Cell Nuclear Antigen; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase