Abstract
Cultured human alveolar macrophages were shown to secrete alpha-2-macroglobulin (α2M), a potent inhibitor of bacterial and mammalian proteases. Secretion could be blocked by 2.0 µg/ml cycloheximide, an inhibitor of protein synthesis. Detection of the inhibitor was achieved by radioimmunoelectrophoresis of concentrated culture medium obtained from cells cultured in the presence of35S-methionine. In addition, concentrated culture medium was treated with antihumanα2M antiserum and antigen: antibody complexes were precipitated with protein A-bearing staphylococci. When the precipitate thus formed was dissolved in a reducing buffer and subjected to SDS electrophoresis, a single radioactive peak of about 185,000 daltons was obtained. This molecular weight corresponds closely to the molecular weight of theα2M subunit. Secretion ofα2M by alveolar macrophages may facilitate the internalization and disposal of proteolytic enzymes in the alveolar microenvironment, and thus play an important role in the defense of the lung.
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References
Benjamin DC, Weimer HE (1966) Synthesis ofα 2AP (acute phase) globulin of rat serum by the liver, Nature 209:1032–1033
Bowden DH, Adamson IYR, Grantham WG, Wyatt JP (1969) Origin of the lung macrophage. Evidence derived from radiation injury. Arch Pathol 88:540–546
Campbell E, White R, Senior R, Rodriquez RJ, Kuhn C (1979) Specific binding and internalization of human neutrophil elastase by human alveolar macrophages. J Clin Inv 64:824–833
Cullen SE, Schwartz BD (1976) An improved method for isolation of H-2 and Ia alloantigens with immunoprecipitation induced by protein A-bearing staphylococci. J Immunol 117:136–142
Debanne MT, Bell R, Dolovich J (1975) Uptake of proteinaseα 2-macroglobulin complexes by alveolar macrophages. Biochim Biophys Acta 411:295–304
Gordon S, Cohn ZA (1973) The Macrophage. In: Annual Review of Cytology 36:171–214
Hall PK, Roberts RC (1978) Physical and chemical properties of human plasmaα 2-macroglobulin. Biochem J 171:27–38
Hovi T, Mosher DF, Vaheri A (1977) Cultured human monocytes synthesize and secreteα 2-macroglobulin. J Exp Med 145:1580–1589
Kaplan J, Neilson ML (1979) Analysis of macrophage surface receptors I. Binding ofα-macroglobulin-protease complexes to rabbit alveolar macrophages. J Biol Chem 254:7323–7328
Kaplan J, Neilson ML (1979) Analysis of macrophage surface receptors II. Internalization ofα-macroglobulin-trypsin complexes by rabbit alveolar macrophages. J Biol Chem 254:7329–7335
Mosher DF, Wing WA (1976) Synthesis and secretion ofα 2-macroglobulin by cultured human fibroblasts. J Exp Med 143:462–467
Mosher DF, Saksela O, Vaheri A (1977) Synthesis of alpha-2-macroglobulin by cultured adherent lung cells. J Clin Invest 60:1036–1045
Nile’hn J-E, Ganrot PO (1967) Plasmin, plasmin inhibitors and degradation products of fibrinogen in human serum, during and after intravenous infusion of steptokinase. Scand J Clin Lab Invest 20:113–121
Pollack A, Gordon S (1975) Scanning electron microscopy of murine macrophages. Surface characteristics during maturation, activation and phagocytosis. Lab Invest 33:469–477
Porzio MA, Pearson AM (1977) Improved resolution of myofibrillar proteins with sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Biochem Biophys Acta 490:27–34
Roberts RC, Riesen WH, Hall PK (1974) Studies on the quaternary structure of human serumα 2-macroglobulin. In: Bayer Symposium V “Protease Inhibitors”. Fritz H, Tscheshce H, Greene LJ, Truscheit E (eds), p. 63–71. Springer, New York
Sancione EJ, Bogden AE (1966) Hepatic synthesis of alpha2 (acute phase)-globulin of rat plasma. Science 153:547–548
Starkey PM, Barrett AJ (1977)α 2-Macroglobulin, a physiological regulator of proteinase activity. In: Proteinases in Mammalian Cells and Tissues. Barrett AJ (ed), p. 663–696. North-Holland, New York
Unkeless JC, Gordon S, Reich E (1974) Secretion of plasminogen activator by stimulated macrophages. J Exp Med 139:834–850
Warr GA, Martin R, Sharp PW, Rossen RO (1977) Normal human bronchial immunoglobulins and proteins. Effects of cigarette smoking. Am Rev Respir Dis 116:25–30
Werb Z, Gordon S (1975) Elastase secretion by stimulated macrophages. Characterization and regulation. J Exp Med 142:361–377
Werb Z, Gordon S (1975) Secretion of specific collagenase by stimulated macrophages. J Exp Med 142:346–360
White R, Lin H-S, Kuhn C (1977) Elastase secretion by peritoneal exudative and alveolar macrophages. J Exp Med 142:802–808
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Supported by grant HL-14262 from the National Heart, Lung and Blood Institute and grant 1143 from the Council for Tobacco Research — USA. Richard White is the recipient of National Heart, Lung and Blood Institute Young Investigators grant HL-24186.
The authors are grateful to Drs. Michael Green and Edward H. Bergofsky (VA Hospital — Northport, N.Y.) for carrying out the bronchopulmonary lavage procedures.
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White, R., Janoff, A. & Godfrey, H.P. Secretion of alpha-2-macroglobulin by human alveolar macrophages. Lung 158, 9–14 (1980). https://doi.org/10.1007/BF02713697
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DOI: https://doi.org/10.1007/BF02713697