Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Mar 1;159(3):844–860. doi: 10.1084/jem.159.3.844

Human pulmonary macrophage-derived mucus secretagogue

PMCID: PMC2187256  PMID: 6699545

Abstract

Human pulmonary macrophages (PM) obtained from surgically removed human lung tissue released a factor after exposure to activated zymosan that caused cultured human airways to release increased amounts of radiolabeled mucous glycoproteins. The factor was released maximally after 4-8 h of zymosan exposure and caused a dose-related increase in glycoprotein release; it was termed macrophage-derived mucus secretagogue (MMS). MMS release was produced in a dose-dependent fashion by activated but not by nonactivated zymosan. The activation of zymosan was C3 dependent, and C3b-coated Sepharose was also an effective stimulant. The data suggested that cell surface activation of the PM was a sufficient stimulus to cause MMS release and that both C3- dependent activation as well as Fc receptor activation were effective. The synthesis of MMS was sensitive to cycloheximide, and no active MMS was detectable intracellularly. To determine if MMS might be one of the oxidative derivatives of arachidonic acid, PM were incubated with cyclooxygenase and lipoxygenase inhibitors before activation. These maneuvers did not influence MMS generation. MMS-rich supernatants were then extracted into organic solvents or exposed to lipophilic resin; in both cases, MMS remained in the aqueous phase. Thus, MMS is not a derivative of arachidonic acid. Sequential fractionation of MMS on ultramembrane and gel filtration followed by isoelectric focusing and gel filtration indicated that MMS is a small (approximately 2000 daltons), acidic (pI, 5.15) molecule. Therefore, surface activation of human PM results in the synthesis and release of a small acidic molecule that causes airway mucous glands to secrete increased quantities of mucous glycoproteins.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boat T. F., Kleinerman J. I. Human respiratory tract secretions. 2. Effect of cholinergic and adrenergic agents on in vitro release of protein and mucous glycoprotein. Chest. 1975 Feb;67(2 Suppl):32S–34S. doi: 10.1378/chest.67.2_supplement.32s. [DOI] [PubMed] [Google Scholar]
  2. Chakrin L. W., Baker A. P., Christian P., Wardell J. R., Jr Effect of cholinergic stimulation on the release of macromolecules by canine trachea in vitro. Am Rev Respir Dis. 1973 Jul;108(1):69–76. doi: 10.1164/arrd.1973.108.1.69. [DOI] [PubMed] [Google Scholar]
  3. Harpel B. M., Kueppers F. Preparative isoelectric focusing with Pevikon as supporting medium. Anal Biochem. 1980 May 1;104(1):173–174. doi: 10.1016/0003-2697(80)90294-8. [DOI] [PubMed] [Google Scholar]
  4. Hocking W. G., Golde D. W. The pulmonary-alveolar macrophage (first of two parts). N Engl J Med. 1979 Sep 13;301(11):580–587. doi: 10.1056/NEJM197909133011104. [DOI] [PubMed] [Google Scholar]
  5. Hunninghake G. W., Gadek J. E., Szapiel S. V., Strumpf I. J., Kawanami O., Ferrans V. J., Keogh B. A., Crystal R. G. The human alveolar macrophage. Methods Cell Biol. 1980;21A:95–105. doi: 10.1016/s0091-679x(08)60760-8. [DOI] [PubMed] [Google Scholar]
  6. Laviolette M., Chang J., Newcombe D. S. Human alveolar macrophages: a lesion in arachidonic acid metabolism in cigarette smokers. Am Rev Respir Dis. 1981 Oct;124(4):397–401. doi: 10.1164/arrd.1981.124.4.397. [DOI] [PubMed] [Google Scholar]
  7. Lemanske R. F., Jr, Joiner K., Kaliner M. The biologic activity of mast cell granules. IV. The effect of complement depletion on rat cutaneous late phase reactions. J Immunol. 1983 Apr;130(4):1881–1884. [PubMed] [Google Scholar]
  8. Marom Z., Shelhamer J. H., Bach M. K., Morton D. R., Kaliner M. Slow-reacting substances, leukotrienes C4 and D4, increase the release of mucus from human airways in vitro. Am Rev Respir Dis. 1982 Sep;126(3):449–451. doi: 10.1164/arrd.1982.126.3.449. [DOI] [PubMed] [Google Scholar]
  9. Marom Z., Shelhamer J. H., Kaliner M. Effects of arachidonic acid, monohydroxyeicosatetraenoic acid and prostaglandins on the release of mucous glycoproteins from human airways in vitro. J Clin Invest. 1981 Jun;67(6):1695–1702. doi: 10.1172/JCI110207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Marom Z., Shelhamer J. H., Sun F., Kaliner M. Human airway monohydroxyeicosatetraenoic acid generation and mucus release. J Clin Invest. 1983 Jul;72(1):122–127. doi: 10.1172/JCI110949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Marvizi S., Melrose R. B. Some spectrally isolated convex planar regions. Proc Natl Acad Sci U S A. 1982 Nov;79(22):7066–7067. doi: 10.1073/pnas.79.22.7066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mason R. J., Stossel T. P., Vaughan M. Lipids of alveolar macrophages, polymorphonuclear leukocytes, and their phagocytic vesicles. J Clin Invest. 1972 Sep;51(9):2399–2407. doi: 10.1172/JCI107052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Metcalfe D. D., Gadek J. E., Raphael G. D., Frank M. M., Kaplan A. P., Kaliner M. Human eosinophil adherence to serum-treated sepharose: granule-associated enzyme release and requirement for activation of the alternative complement pathway. J Immunol. 1977 Nov;119(5):1744–1750. [PubMed] [Google Scholar]
  14. Rouzer C. A., Scott W. A., Cohn Z. A., Blackburn P., Manning J. M. Mouse peritoneal macrophages release leukotriene C in response to a phagocytic stimulus. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4928–4932. doi: 10.1073/pnas.77.8.4928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Shelhamer J. H., Marom Z., Kaliner M. Immunologic and neuropharmacologic stimulation of mucous glycoprotein release from human airways in vitro. J Clin Invest. 1980 Dec;66(6):1400–1408. doi: 10.1172/JCI109993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Steel L., Kaliner M. Prostaglandin-generating factor of anaphylaxis. Identification and isolation. J Biol Chem. 1981 Dec 25;256(24):12692–12698. [PubMed] [Google Scholar]
  17. Sturgess J., Reid L. An organ culture study of the effect of drugs on the secretory activity of the human bronchial submucosal gland. Clin Sci. 1972 Oct;43(4):533–543. doi: 10.1042/cs0430533. [DOI] [PubMed] [Google Scholar]
  18. Ueki I., German V. F., Nadel J. A. Micropipette measurement of airway submucosal gland secretion. Autonomic effects. Am Rev Respir Dis. 1980 Feb;121(2):351–357. doi: 10.1164/arrd.1980.121.2.351. [DOI] [PubMed] [Google Scholar]
  19. Wessells N. K., Spooner B. S., Ash J. F., Bradley M. O., Luduena M. A., Taylor E. L., Wrenn J. T., Yamada K. Microfilaments in cellular and developmental processes. Science. 1971 Jan 15;171(3967):135–143. doi: 10.1126/science.171.3967.135. [DOI] [PubMed] [Google Scholar]
  20. Zurier R. B., Hoffstein S., Weissmann G. Cytochalasin B: effect on lysosomal enzyme release from human leukocytes. Proc Natl Acad Sci U S A. 1973 Mar;70(3):844–848. doi: 10.1073/pnas.70.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES