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. 1990 Sep;87(17):6813–6817. doi: 10.1073/pnas.87.17.6813

Interleukin 3 and granulocyte/macrophage-colony-stimulating factor render human basophils responsive to low concentrations of complement component C3a.

S C Bischoff 1, A L de Weck 1, C A Dahinden 1
PMCID: PMC54628  PMID: 1697689

Abstract

Complement component C3a is an anaphylatoxin known to induce plasma exudation and smooth muscle contraction in tissues. The effects on inflammatory effector leukocytes, however, are poorly defined and controversial, being at best weak and occurring at very high C3a concentrations. Here, we examined the effect of C3a upon mediator release from human basophils, with and without pretreatment with interleukin 3 (IL-3), a hematopoietic growth factor recently found to profoundly modify the basophil response to various cell agonists. In the absence of cytokines, C3a, even at a concentration of 1 microM, was ineffective or only weakly stimulatory for basophil mediator release. However, when basophils were pretreated with IL-3 at concentrations of only 0.01-1 unit/ml, they became responsive to C3a, releasing large amounts of histamine and also generating leukotrienes. Surprisingly, almost optimal effects occurred with even very low C3a concentrations (1 nM). Another hematopoietic growth factor, granulocyte/macrophage-colony-stimulating factor (GM-CSF), was also found to render basophils capable of responding to C3a, but the effect was weaker than that of IL-3. C3a-induced histamine release and leukotriene generation occurred rapidly in IL-3-primed cells, being complete after 0.5 and 2 min, respectively. The rapid and strong degranulation response, occurring at very low concentrations of C3a, suggests the presence of a high-affinity C3a receptor on basophils, which might be inducible by cytokines. Our results demonstrate that, depending on the presence of IL-3 or GM-CSF, C3a is a potent basophil activator, and such a phenomenon could be of relevance in various inflammatory processes, especially hypersensitivity reactions.

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Selected References

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  1. Cochrane C. G., Müller-Eberhard H. J. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med. 1968 Feb 1;127(2):371–386. doi: 10.1084/jem.127.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dahinden C. A., Kurimoto J., Baggiolini M., Dewald B., Walz A. Histamine and sulfidoleukotriene release from human basophils: different effects of antigen, anti-IgE, C5a, f-Met-Leu-Phe and the novel neutrophil-activating peptide NAF. Int Arch Allergy Appl Immunol. 1989;90(2):113–118. doi: 10.1159/000235011. [DOI] [PubMed] [Google Scholar]
  3. Dahinden C. A., Kurimoto Y., De Weck A. L., Lindley I., Dewald B., Baggiolini M. The neutrophil-activating peptide NAF/NAP-1 induces histamine and leukotriene release by interleukin 3-primed basophils. J Exp Med. 1989 Nov 1;170(5):1787–1792. doi: 10.1084/jem.170.5.1787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fernandez H. N., Henson P. M., Otani A., Hugli T. E. Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol. 1978 Jan;120(1):109–115. [PubMed] [Google Scholar]
  5. Glovsky M. M., Hugli T. E., Ishizaka T., Lichtenstein L. M., Erickson B. W. Anaphylatoxin-induced histamine release with human leukocytes: studies of C3a leukocyte binding and histamine release. J Clin Invest. 1979 Sep;64(3):804–811. doi: 10.1172/JCI109527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Grant J. A., Lett-Brown M. A., Warner J. A., Plaut M., Lichtenstein L. M., Haak-Frendscho M., Kaplan A. P. Activation of basophils. Fed Proc. 1986 Oct;45(11):2653–2658. [PubMed] [Google Scholar]
  7. Hartman C. T., Jr, Glovsky M. M. Complement activation requirements for histamine release from human leukocytes: influence of purified C3ahu and C5ahu on histamine release. Int Arch Allergy Appl Immunol. 1981;66(3):274–281. doi: 10.1159/000232831. [DOI] [PubMed] [Google Scholar]
  8. Hirai K., Morita Y., Misaki Y., Ohta K., Takaishi T., Suzuki S., Motoyoshi K., Miyamoto T. Modulation of human basophil histamine release by hemopoietic growth factors. J Immunol. 1988 Dec 1;141(11):3958–3964. [PubMed] [Google Scholar]
  9. Hong C. S., Stadler B. M., Wälti M., De Weck A. L. Dot-immunobinding assay with monoclonal anti-IgE antibodies for the detection and quantitation of human IgE. J Immunol Methods. 1986 Dec 24;95(2):195–202. doi: 10.1016/0022-1759(86)90406-0. [DOI] [PubMed] [Google Scholar]
  10. Hugli T. E., Gerard C., Kawahara M., Scheetz M. E., 2nd, Barton R., Briggs S., Koppel G., Russell S. Isolation of three separate anaphylatoxins from complement-activated human serum. Mol Cell Biochem. 1981 Dec 4;41:59–66. doi: 10.1007/BF00225297. [DOI] [PubMed] [Google Scholar]
  11. Hugli T. E. Human anaphylatoxin (C3a) from the third component of complement. Primary structure. J Biol Chem. 1975 Nov 10;250(21):8293–8301. [PubMed] [Google Scholar]
  12. Hugli T. E., Müller-Eberhard H. J. Anaphylatoxins: C3a and C5a. Adv Immunol. 1978;26:1–53. doi: 10.1016/s0065-2776(08)60228-x. [DOI] [PubMed] [Google Scholar]
  13. Kurimoto Y., de Weck A. L., Dahinden C. A. Interleukin 3-dependent mediator release in basophils triggered by C5a. J Exp Med. 1989 Aug 1;170(2):467–479. doi: 10.1084/jem.170.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Naclerio R. M., Proud D., Togias A. G., Adkinson N. F., Jr, Meyers D. A., Kagey-Sobotka A., Plaut M., Norman P. S., Lichtenstein L. M. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med. 1985 Jul 11;313(2):65–70. doi: 10.1056/NEJM198507113130201. [DOI] [PubMed] [Google Scholar]
  15. Nagata S., Glovsky M. M., Kunkel S. L. Anaphylatoxin-induced neutrophil chemotaxis and aggregation. Limited aggregation and specific desensitization induced by human C3a and synthetic C3a octapeptides. Int Arch Allergy Appl Immunol. 1987;82(1):4–9. doi: 10.1159/000234281. [DOI] [PubMed] [Google Scholar]
  16. Schleimer R. P., Derse C. P., Friedman B., Gillis S., Plaut M., Lichtenstein L. M., MacGlashan D. W., Jr Regulation of human basophil mediator release by cytokines. I. Interaction with antiinflammatory steroids. J Immunol. 1989 Aug 15;143(4):1310–1317. [PubMed] [Google Scholar]
  17. Schwartz L. B., Kawahara M. S., Hugli T. E., Vik D., Fearon D. T., Austen K. F. Generation of C3a anaphylatoxin from human C3 by human mast cell tryptase. J Immunol. 1983 Apr;130(4):1891–1895. [PubMed] [Google Scholar]
  18. 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]
  19. Tonks N. K., Charbonneau H. Protein tyrosine dephosphorylation and signal transduction. Trends Biochem Sci. 1989 Dec;14(12):497–500. doi: 10.1016/0968-0004(89)90184-9. [DOI] [PubMed] [Google Scholar]
  20. Valent P., Besemer J., Muhm M., Majdic O., Lechner K., Bettelheim P. Interleukin 3 activates human blood basophils via high-affinity binding sites. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5542–5546. doi: 10.1073/pnas.86.14.5542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vallota E. H., Müller-Eberhard H. J. Formation of C3a and C5a anaphylatoxins in whole human serum after inhibition of the anaphylatoxin inactivator. J Exp Med. 1973 May 1;137(5):1109–1123. doi: 10.1084/jem.137.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wuepper K. D., Bokisch V. A., Müller-Eberhard H. J., Stoughton R. B. Cutaneous responses to human C 3 anaphylatoxin in man. Clin Exp Immunol. 1972 May;11(1):13–20. [PMC free article] [PubMed] [Google Scholar]
  23. Yarden Y., Ullrich A. Growth factor receptor tyrosine kinases. Annu Rev Biochem. 1988;57:443–478. doi: 10.1146/annurev.bi.57.070188.002303. [DOI] [PubMed] [Google Scholar]

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