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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Aug;79(15):4665–4667. doi: 10.1073/pnas.79.15.4665

Generation of leukotriene C4 from a subclass of mast cells differentiated in vitro from mouse bone marrow.

E Razin, J M Mencia-Huerta, R A Lewis, E J Corey, K F Austen
PMCID: PMC346736  PMID: 6126876

Abstract

Bone marrow-derived mast cells, differentiated in vitro, demonstrate surface IgE, receptors and contain histamine in metachromatic granules, which are composed of chondroitin sulfate E proteoglycan rather than heparin proteoglycan. Activation of this subclass of mast cells with calcium ionophore A23187 resulted in generation of immunoreactive C-6-sulfidopeptide leukotriene in a dose- and time-dependent fashion. Isolation of immunoreactive C-6-sulfldopeptide leukotriene by reverse-phase high-performance liquid chromatography (RP-HPLC) revealed a retention time and a specific biologic activity identical to those of synthetic leukotriene C4 (LTC4). Neither radiolabeled nor immunoreactive conversion products of [3H]LTC4/LTC4 were recognized during RP-HPLC resolution of the supernatants. The failure of fresh bone marrow cultures to generate C-6-sulfidopeptide leukotriene in response to ionophore indicates that leukotriene generation is dependent upon cellular differentiation into a mast cell population. The amount of LTC4 generated during optimal ionophore stimulation, 90.9 +/- 7.5 ng per 10(6) cells, contrasts with the relatively low amounts of C-6-sulfidopeptide leukotriene generated by the conventional heparin-containing rat mast cells or mouse mastocytoma cells.

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Selected References

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

  1. BROCKLEHURST W. E. The release of histamine and formation of a slow-reacting substance (SRS-A) during anaphylactic shock. J Physiol. 1960 Jun;151:416–435. doi: 10.1113/jphysiol.1960.sp006449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Levine L., Morgan R. A., Lewis R. A., Austen K. F., Clark D. A., Marfat A., Corey E. J. Radioimmunoassay of the leukotrienes of slow reacting substance of anaphylaxis. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7692–7696. doi: 10.1073/pnas.78.12.7692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Lewis R. A., Austen K. F., Drazen J. M., Clark D. A., Marfat A., Corey E. J. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3710–3714. doi: 10.1073/pnas.77.6.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Lewis R. A., Austen K. F. Mediation of local homeostasis and inflammation by leukotrienes and other mast cell-dependent compounds. Nature. 1981 Sep 10;293(5828):103–108. doi: 10.1038/293103a0. [DOI] [PubMed] [Google Scholar]
  5. Lewis R. A., Drazen J. M., Austen K. F., Clark D. A., Corey E. J. Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis-geometry for biological activity. Biochem Biophys Res Commun. 1980 Sep 16;96(1):271–277. doi: 10.1016/0006-291x(80)91210-3. [DOI] [PubMed] [Google Scholar]
  6. Lewis R. A., Wasserman S. I., Goetzi E. J., Austen K. F. Formation of slow-reacting substance of anaphylaxis in human lung tissue and cells before release. J Exp Med. 1974 Nov 1;140(5):1133–1146. doi: 10.1084/jem.140.5.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Metcalfe D. D., Lewis R. A., Silbert J. E., Rosenberg R. D., Wasserman S. I., Austen K. F. Isolation and characterization of heparin from human lung. J Clin Invest. 1979 Dec;64(6):1537–1543. doi: 10.1172/JCI109613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Metcalfe D. D., Wasserman S. I., Austen K. F. Isolation and characterization of sulphated mucopolysaccharides from rat leukaemic (RBL-1) basophils. Biochem J. 1980 Feb 1;185(2):367–372. doi: 10.1042/bj1850367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Morris H. R., Taylor G. W., Piper P. J., Tippins J. R. Structure of slow-reacting substance of anaphylaxis from guinea-pig lung. Nature. 1980 May 8;285(5760):104–106. doi: 10.1038/285104a0. [DOI] [PubMed] [Google Scholar]
  10. Murphy R. C., Hammarström S., Samuelsson B. Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4275–4279. doi: 10.1073/pnas.76.9.4275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Orenstein N. S., Galli S. J., Dvorak A. M., Silbert J. E., Dvorak H. F. Sulfated glycosaminoglycans of guinea pig basophilic leukocytes. J Immunol. 1978 Aug;121(2):586–592. [PubMed] [Google Scholar]
  12. Orning L., Hammarström S. Inhibition of leukotriene C and leukotriene D biosynthesis. J Biol Chem. 1980 Sep 10;255(17):8023–8026. [PubMed] [Google Scholar]
  13. Razin E., Cordon-Cardo C., Good R. A. Growth of a pure population of mouse mast cells in vitro with conditioned medium derived from concanavalin A-stimulated splenocytes. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2559–2561. doi: 10.1073/pnas.78.4.2559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Razin E., Stevens R. L., Akiyama F., Schmid K., Austen K. F. Culture from mouse bone marrow of a subclass of mast cells possessing a distinct chondroitin sulfate proteoglycan with glycosaminoglycans rich in N-acetylgalactosamine-4,6-disulfate. J Biol Chem. 1982 Jun 25;257(12):7229–7236. [PubMed] [Google Scholar]
  15. Schrader J. W., Lewis S. J., Clark-Lewis I., Culvenor J. G. The persisting (P) cell: histamine content, regulation by a T cell-derived factor, origin from a bone marrow precursor, and relationship to mast cells. Proc Natl Acad Sci U S A. 1981 Jan;78(1):323–327. doi: 10.1073/pnas.78.1.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tertian G., Yung Y. P., Guy-Grand D., Moore M. A. Long-term in vitro culture of murine mast cells. I. Description of a growth factor-dependent culture technique. J Immunol. 1981 Aug;127(2):788–794. [PubMed] [Google Scholar]
  17. Yecies L. D., Wedner H. J., Johnson S. M., Jakschik B. A., Parker C. W. Slow reacting substance (SRS) from ionophore A23187-stimulated peritoneal mast cells of the normal rat. I. Conditions of generation and initial characterization. J Immunol. 1979 May;122(5):2083–2089. [PubMed] [Google Scholar]
  18. Yung Y. P., Eger R., Tertian G., Moore M. A. Long-term in vitro culture of murine mast cells. II. Purification of a mast cell growth factor and its dissociation from TCGF. J Immunol. 1981 Aug;127(2):794–799. [PubMed] [Google Scholar]
  19. Yurt R. W., Leid R. W., Jr, Austen K. F. Native heparin from rat peritoneal mast cells. J Biol Chem. 1977 Jan 25;252(2):518–521. [PubMed] [Google Scholar]

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