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 pepti des, 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 co mparison to chromogranin A (CGA), a marker of differentiated neuroendo crine cells, and proliferating cell nuclear antigen (PCNA), which is e xpressed by actively dividing cells. PGP 9.5 immunostaining colocalize d with CGA in many cells, although the peak abundance of PGP 9.5 prece ded that of CGA by 4 to 6 weeks. In addition, a novel staining pattern was noted for PGP 9.5: diffuse cytoplasmic staining of undifferentiat ed epithelial cells, which was demonstrated by all of the airways befo re 15 weeks gestation. After gestational week 15, only the smallest ai rways demonstrated this pattern. PCNA immunostaining demonstrated age- dependent regional variation. All samples had approximately 25% epithe lial 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 th at for PCNA, although PGP 9.5 positive cells were usually PCNA negativ e. These observations suggest that other growth factors produced by ne uroendocrine epithelial cells also participate in lung development. (C ) 1997 Wiley-Liss, Inc.