Although synthesis of immunoglobulins by cells in the human lower respiratory tract has never been directly demonstrated, local production of immunoglobulins by cells within lung parenchyma is thought to play an important role in protecting the normal human lung against a variety of pathogenic organisms, and may contribute to the development of some interstitial lung diseases. To determine whether or not the epithelial surface of the human lower respiratory tract is a site of immunoglobulin synthesis, immunoglobulin production by cells recovered by bronchoalveolar lavage and lung parenchymal tissue from normal subjects and patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis was evaluated using a reverse hemolytic plaque assay and by measuring incorporation of [35S]methionine into immunoglobulins. Although the reverse hemolytic plaque assay demonstrated immunoglobulin-releasing cells to be present on the surface of the lower respiratory tract of normal subjects, and present in increased numbers in patients with IPF or sarcoidosis, these plaque-forming cells were not actively synthesizing immunoglobulins, since preincubation of lavage cells in order to remove immunoglobulin bound to the surface of the cells reduced the number of plaque-forming cells, and inhibition of protein synthesis by cycloheximide did not further reduce the number of plaque-forming cells. Furthermore, direct evaluation of immunoglobulin synthesis using radiolabeling, immunoprecipitation and SDS-polyacrylamide gel electrophoresis failed to detect de novo IgG production by cells recovered from the alveolar surface of 15 of 17 subjects, IgM by 17 of 17, and IgA by 16 of 17. Of the few instances in which de novo immunoglobulin production was detected (IgG sarcoid, n = 1; IgG IPF, n = 1; IgA IPF, n = 1), it was very minimal. In contrast, lung parenchymal tissue from patients with sarcoidosis actively incorporated [35S]methionine into immunoglobulins in amounts that could only be explained by the de novo immunoglobulin synthesis by B-lymphocytes present in the lung tissue. Together, these observations suggest that the human lower respiratory tract is a site of immunoglobulin synthesis, but little if any de novo immunoglobulin synthesis occurs on the epithelial surface.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine