Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1985 Apr 1;161(4):657–668. doi: 10.1084/jem.161.4.657

Anaphylatoxin C3a enhances mucous glycoprotein release from human airways in vitro

PMCID: PMC2189058  PMID: 2580036

Abstract

Because C3a may be generated during the course of pulmonary inflammatory reactions, we investigated the ability of C3a to affect mucous glycoprotein (MGP) secretion from cultured human airways. C3a, but not C3a des Arg, caused a dose-related increase in MGP release (maximal after 4-6 h), with as little as 15 micrograms of C3a per milliliter stimulating a 40% increase. The experimental evidence suggested that immunologically specific C3a was required for the secretagogue actions, as monospecific anti-C3a inhibited the reaction, as well as specifically absorbing the secretagogue from solution. Moreover, it appeared that C3a does not require mast cell activation, eicosanoid generation, or macrophage-derived mucus secretagogue synthesis for its effect, since (a) no evidence of histamine release accompanied C3a-induced MGP release, and dibutyryl cAMP failed to affect C3a-induced MGP release, while reducing the actions of reversed anaphylaxis; (b) MGP release caused by C3a was not influenced by eicosatetraynoic acid or specific cyclooxygenase inhibitors, and no leukotrienes were detectable on the supernatants of C3a-stimulated airways; and (c) cycloheximide failed to affect C3a secretion- stimulating actions. Thus, C3a is a potent mucus secretagogue, and, possibly, acts directly as a glandular stimulant. It seems likely that C3a generated in the course of pulmonary inflammation might contribute to the mucus secretion associated with pulmonary infections.

Full Text

The Full Text of this article is available as a PDF (727.4 KB).

Selected References

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

  1. Berger M., Gaither T. A., Hammer C. H., Frank M. M. Lack of binding of human C3, in its native state, to C3b receptors. J Immunol. 1981 Oct;127(4):1329–1334. [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. Chalon J., Tayyab M. A., Ramanathan S. Cytology of respiratory epithelium as a predictor of respiratory complications after operation. Chest. 1975 Jan;67(1):32–35. doi: 10.1378/chest.67.1.32. [DOI] [PubMed] [Google Scholar]
  4. Damerau B., Grünefeld E., Vogt W. Aggregation of leukocytes induced by the complement-derived peptides C3a and C5a and by three synthetic formyl-methionyl peptides. Int Arch Allergy Appl Immunol. 1980;63(2):159–169. doi: 10.1159/000232622. [DOI] [PubMed] [Google Scholar]
  5. Hammer C. H., Wirtz G. H., Renfer L., Gresham H. D., Tack B. F. Large scale isolation of functionally active components of the human complement system. J Biol Chem. 1981 Apr 25;256(8):3995–4006. [PubMed] [Google Scholar]
  6. Hartung H. P., Bitter-Suermann D., Hadding U. Induction of thromboxane release from macrophages by anaphylatoxic peptide C3a of complement and synthetic hexapeptide C3a 72-77. J Immunol. 1983 Mar;130(3):1345–1349. [PubMed] [Google Scholar]
  7. Hugli T. E. The structural basis for anaphylatoxin and chemotactic functions of C3a, C4a, and C5a. Crit Rev Immunol. 1981 Feb;1(4):321–366. [PubMed] [Google Scholar]
  8. Imagawa D. K., Osifchin N. E., Paznekas W. A., Shin M. L., Mayer M. M. Consequences of cell membrane attack by complement: release of arachidonate and formation of inflammatory derivatives. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6647–6651. doi: 10.1073/pnas.80.21.6647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson A. R., Hugli T. E., Müller-Eberhard H. J. Release of histamine from rat mast cells by the complement peptides C3a and C5a. Immunology. 1975 Jun;28(6):1067–1080. [PMC free article] [PubMed] [Google Scholar]
  10. Joiner K. A., Brown E. J., Frank M. M. Complement and bacteria: chemistry and biology in host defense. Annu Rev Immunol. 1984;2:461–491. doi: 10.1146/annurev.iy.02.040184.002333. [DOI] [PubMed] [Google Scholar]
  11. Madsen L. H., Rodkey L. S. A method for preparing IgG F(ab')2 fragments using small amounts of serum. J Immunol Methods. 1976;9(3-4):355–361. doi: 10.1016/0022-1759(76)90210-6. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Marom Z., Shelhamer J. H., Kaliner M. Human monocyte-derived mucus secretagogue. J Clin Invest. 1985 Jan;75(1):191–198. doi: 10.1172/JCI111674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Marom Z., Shelhamer J. H., Kaliner M. Human pulmonary macrophage-derived mucus secretagogue. J Exp Med. 1984 Mar 1;159(3):844–860. doi: 10.1084/jem.159.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Metz S. A., Hall M. E., Harper T. W., Murphy R. C. Rapid extraction of leukotrienes from biologic fluids and quantitation by high-performance liquid chromatography. J Chromatogr. 1982 Dec 10;233:193–201. doi: 10.1016/s0378-4347(00)81746-6. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Showell H. J., Glovsky M. M., Ward P. A. C3a-induced lysosomal enzyme secretion from human neutrophils: lack of inhibition by f met-leu-phe antagonists and inhibition by arachidonic acid antagonists. Int Arch Allergy Appl Immunol. 1982;67(3):227–232. doi: 10.1159/000233023. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Stenson W. F., Parker C. W. Prostaglandins, macrophages, and immunity. J Immunol. 1980 Jul;125(1):1–5. [PubMed] [Google Scholar]
  22. Stimler N. P., Bach M. K., Bloor C. M., Hugli T. E. Release of leukotrienes from guinea pig lung stimulated by C5ades Arg anaphylatoxin. J Immunol. 1982 May;128(5):2247–2252. [PubMed] [Google Scholar]
  23. Stimler N. P., Hugli T. E., Bloor C. M. Pulmonary injury induced by C3a and C5a anaphylatoxins. Am J Pathol. 1980 Aug;100(2):327–348. [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Yecies L. D., Johnson S. M., Wedner H. J., Parker C. W. Slow reacting substance (SRS) from ionophore A23187-stimulated peritoneal mast cells of the normal rat. II. Evidence for a precursor role of arachidonic acid and further purification. J Immunol. 1979 May;122(5):2090–2095. [PubMed] [Google Scholar]
  27. Zimmer B., Hartung H. P., Scharfenberger G., Bitter-Suermann D., Hadding U. Quantitative studies of the secretion of complement component C3 by resident, elicited and activated macrophages. Comparison with C2, C4 and lysosomal enzyme release. Eur J Immunol. 1982 May;12(5):426–430. doi: 10.1002/eji.1830120513. [DOI] [PubMed] [Google Scholar]

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

RESOURCES