Changes in the Cell Surface Protein Composition of Human Alveolar Macrophages Induced by Smoking

Abstract

The cell surface proteins of human alveolar macrophages obtained from nonsmokers have been compared to those of alveolar macrophages obtained from smokers. Proteins of nonsmokers' alveolar macrophages surface labeled with ¹²⁵I differed from those of smokers' alveolar macrophages, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three major radiolabeled proteins with molecular weights of 183,000, 80,000, and 30,000 were identified in fresh smokers' cells. The major radiolabeled protein of nonsmokers' macrophages had an apparent molecular weight of ∼183,000. Affinity chromatography suggested the M_r 183,000 protein is a mannose receptor. In contrast, the molecular weight of the major radiolabeled protein of smokers' alveolar macrophages was ∼30,000; the M_r 183,000 protein was less prominent. When nonsmokers' alveolar macrophages were cultured in vitro before ¹²⁵I labeling, the cell surface protein pattern changed to resemble that of smokers' alveolar macrophages; the M_r 183,000 protein could no longer be detected on the cell surface, whereas a M_r 80,000 protein was increased in quantity and a new M_r 30,000 protein was detected. Nonadherent macrophages showed similar changes in their surface-labeled proteins but also contained a new prominently labeled M_r 70,000 protein. Limited proteolysis peptide mapping with five different enzymes did not reveal any evidence of homology among the M_r 183,000, 80,000, 70,000, and 30,000 proteins. The differences in cell surface protein composition between alveolar macrophages of smokers and nonsmokers may reflect their functional capabilities or their state of “activation” and may be mechanistically important in the development of various pulmonary diseases seen in smokers including cancer. These results also demonstrate that major changes in the surface proteins of the human alveolar macrophage plasma membrane can occur rapidly following manipulation.