Abstract
Mast cells (MC) play a central role in extrinsic allergic reactions such as asthma and may participate in other inflammatory and fibrotic processes. However, with the exception of immunoglobulin E (IgE) receptor-dependent stimulation, no secretagogues of human lung MC have yet been described. It is also unclear whether mediator release can be regulated by certain cytokines as demonstrated previously in basophils and other human inflammatory effector cells. Here, we show that the c- kit ligand (KL), a recently identified stem cell growth factor, at concentrations 10-100 times lower than that required to promote cell proliferation, enhances the release of histamine and leukotriene C4 in response to IgE receptor crosslinking of human lung MC. KL does not induce mediator release per se, but increases the sensitivity of MC to anti-IgE receptor stimulation and also enhances mediator release to maximally effective concentrations of anti-IgE receptor antibody. By contrast, a large number of cytokines examined, including the mast cell growth factors/agonists in rodents, interleukin 3 (IL-3), IL-4, IL-9, and nerve growth factor, were ineffective in this respect. These findings suggest a unique role of KL in regulating effector functions of human mucosal MC.
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- Anderson D. M., Lyman S. D., Baird A., Wignall J. M., Eisenman J., Rauch C., March C. J., Boswell H. S., Gimpel S. D., Cosman D. Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell. 1990 Oct 5;63(1):235–243. doi: 10.1016/0092-8674(90)90304-w. [DOI] [PubMed] [Google Scholar]
- Ashman L. K., Cambareri A. C., To L. B., Levinsky R. J., Juttner C. A. Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow. Blood. 1991 Jul 1;78(1):30–37. [PubMed] [Google Scholar]
- Benyon R. C., Lowman M. A., Church M. K. Human skin mast cells: their dispersion, purification, and secretory characterization. J Immunol. 1987 Feb 1;138(3):861–867. [PubMed] [Google Scholar]
- Bernstein I. D., Andrews R. G., Zsebo K. M. Recombinant human stem cell factor enhances the formation of colonies by CD34+ and CD34+lin- cells, and the generation of colony-forming cell progeny from CD34+lin- cells cultured with interleukin-3, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Blood. 1991 Jun 1;77(11):2316–2321. [PubMed] [Google Scholar]
- Bienenstock J., Tomioka M., Matsuda H., Stead R. H., Quinonez G., Simon G. T., Coughlin M. D., Denburg J. A. The role of mast cells in inflammatory processes: evidence for nerve/mast cell interactions. Int Arch Allergy Appl Immunol. 1987;82(3-4):238–243. doi: 10.1159/000234197. [DOI] [PubMed] [Google Scholar]
- Bischoff S. C., Brunner T., De Weck A. L., Dahinden C. A. Interleukin 5 modifies histamine release and leukotriene generation by human basophils in response to diverse agonists. J Exp Med. 1990 Dec 1;172(6):1577–1582. doi: 10.1084/jem.172.6.1577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bischoff S. C., de Weck A. L., Dahinden C. A. Interleukin 3 and granulocyte/macrophage-colony-stimulating factor render human basophils responsive to low concentrations of complement component C3a. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6813–6817. doi: 10.1073/pnas.87.17.6813. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Broxmeyer H. E., Cooper S., Lu L., Hangoc G., Anderson D., Cosman D., Lyman S. D., Williams D. E. Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells. Blood. 1991 May 15;77(10):2142–2149. [PubMed] [Google Scholar]
- Brunner T., de Weck A. L., Dahinden C. A. Platelet-activating factor induces mediator release by human basophils primed with IL-3, granulocyte-macrophage colony-stimulating factor, or IL-5. J Immunol. 1991 Jul 1;147(1):237–242. [PubMed] [Google Scholar]
- 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]
- Dahinden C. A., Zingg J., Maly F. E., de Weck A. L. Leukotriene production in human neutrophils primed by recombinant human granulocyte/macrophage colony-stimulating factor and stimulated with the complement component C5A and FMLP as second signals. J Exp Med. 1988 Apr 1;167(4):1281–1295. doi: 10.1084/jem.167.4.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flanagan J. G., Leder P. The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell. 1990 Oct 5;63(1):185–194. doi: 10.1016/0092-8674(90)90299-t. [DOI] [PubMed] [Google Scholar]
- Fujisawa T., Abu-Ghazaleh R., Kita H., Sanderson C. J., Gleich G. J. Regulatory effect of cytokines on eosinophil degranulation. J Immunol. 1990 Jan 15;144(2):642–646. [PubMed] [Google Scholar]
- Hempstead B. L., Martin-Zanca D., Kaplan D. R., Parada L. F., Chao M. V. High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature. 1991 Apr 25;350(6320):678–683. doi: 10.1038/350678a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Huang E., Nocka K., Beier D. R., Chu T. Y., Buck J., Lahm H. W., Wellner D., Leder P., Besmer P. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell. 1990 Oct 5;63(1):225–233. doi: 10.1016/0092-8674(90)90303-v. [DOI] [PubMed] [Google Scholar]
- Ishizaka T., Conrad D. H., Schulman E. S., Sterk A. R., Ishizaka K. Biochemical analysis of initial triggering events of IgE-mediated histamine release from human lung mast cells. J Immunol. 1983 May;130(5):2357–2362. [PubMed] [Google Scholar]
- Kanakura Y., Druker B., Cannistra S. A., Furukawa Y., Torimoto Y., Griffin J. D. Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves tyrosine phosphorylation of a common set of cytoplasmic proteins. Blood. 1990 Aug 15;76(4):706–715. [PubMed] [Google Scholar]
- Klein R., Jing S. Q., Nanduri V., O'Rourke E., Barbacid M. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell. 1991 Apr 5;65(1):189–197. doi: 10.1016/0092-8674(91)90419-y. [DOI] [PubMed] [Google Scholar]
- Kurimoto Y., De Weck A. L., Dahinden C. A. The effect of interleukin 3 upon IgE-dependent and IgE-independent basophil degranulation and leukotriene generation. Eur J Immunol. 1991 Feb;21(2):361–368. doi: 10.1002/eji.1830210217. [DOI] [PubMed] [Google Scholar]
- 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]
- Levi-Schaffer F., Austen K. F., Caulfield J. P., Hein A., Gravallese P. M., Stevens R. L. Co-culture of human lung-derived mast cells with mouse 3T3 fibroblasts: morphology and IgE-mediated release of histamine, prostaglandin D2, and leukotrienes. J Immunol. 1987 Jul 15;139(2):494–500. [PubMed] [Google Scholar]
- MacGlashan D. W., Jr, Schleimer R. P., Peters S. P., Schulman E. S., Adams G. K., Sobotka A. K., Newball H. H., Lichtenstein L. M. Comparative studies of human basophils and mast cells. Fed Proc. 1983 May 15;42(8):2504–2509. [PubMed] [Google Scholar]
- Martin F. H., Suggs S. V., Langley K. E., Lu H. S., Ting J., Okino K. H., Morris C. F., McNiece I. K., Jacobsen F. W., Mendiaz E. A. Primary structure and functional expression of rat and human stem cell factor DNAs. Cell. 1990 Oct 5;63(1):203–211. doi: 10.1016/0092-8674(90)90301-t. [DOI] [PubMed] [Google Scholar]
- Massey W. A., Randall T. C., Kagey-Sobotka A., Warner J. A., MacDonald S. M., Gillis S., Allison A. C., Lichtenstein L. M. Recombinant human IL-1 alpha and -1 beta potentiate IgE-mediated histamine release from human basophils. J Immunol. 1989 Sep 15;143(6):1875–1880. [PubMed] [Google Scholar]
- Mayrhofer G., Gadd S. J., Spargo L. D., Ashman L. K. Specificity of a mouse monoclonal antibody raised against acute myeloid leukaemia cells for mast cells in human mucosal and connective tissues. Immunol Cell Biol. 1987 Jun;65(Pt 3):241–250. doi: 10.1038/icb.1987.27. [DOI] [PubMed] [Google Scholar]
- Pearce F. L., Thompson H. L. Some characteristics of histamine secretion from rat peritoneal mast cells stimulated with nerve growth factor. J Physiol. 1986 Mar;372:379–393. doi: 10.1113/jphysiol.1986.sp016014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rothe M. J., Nowak M., Kerdel F. A. The mast cell in health and disease. J Am Acad Dermatol. 1990 Oct;23(4 Pt 1):615–624. doi: 10.1016/0190-9622(90)70264-i. [DOI] [PubMed] [Google Scholar]
- Salari H., Chan-Yeung M. Interleukin-1 potentiates antigen-mediated arachidonic acid metabolite formation in mast cells. Clin Exp Allergy. 1989 Nov;19(6):637–641. doi: 10.1111/j.1365-2222.1989.tb02760.x. [DOI] [PubMed] [Google Scholar]
- Schleimer R. P., Fox C. C., Naclerio R. M., Plaut M., Creticos P. S., Togias A. G., Warner J. A., Kagey-Sobotka A., Lichtenstein L. M. Role of human basophils and mast cells in the pathogenesis of allergic diseases. J Allergy Clin Immunol. 1985 Aug;76(2 Pt 2):369–374. doi: 10.1016/0091-6749(85)90656-6. [DOI] [PubMed] [Google Scholar]
- Schleimer R. P., MacGlashan D. W., Jr, Peters S. P., Pinckard R. N., Adkinson N. F., Jr, Lichtenstein L. M. Characterization of inflammatory mediator release from purified human lung mast cells. Am Rev Respir Dis. 1986 Apr;133(4):614–617. doi: 10.1164/arrd.1986.133.4.614. [DOI] [PubMed] [Google Scholar]
- Schulman E. S., MacGlashan D. W., Jr, Peters S. P., Schleimer R. P., Newball H. H., Lichtenstein L. M. Human lung mast cells: purification and characterization. J Immunol. 1982 Dec;129(6):2662–2667. [PubMed] [Google Scholar]
- Schulman E. S., Post T. J., Henson P. M., Giclas P. C. Differential effects of the complement peptides, C5a and C5a des Arg on human basophil and lung mast cell histamine release. J Clin Invest. 1988 Mar;81(3):918–923. doi: 10.1172/JCI113403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevens R. L., Austen K. F. Recent advances in the cellular and molecular biology of mast cells. Immunol Today. 1989 Nov;10(11):381–386. doi: 10.1016/0167-5699(89)90272-7. [DOI] [PubMed] [Google Scholar]
- Takafuji S., Bischoff S. C., De Weck A. L., Dahinden C. A. IL-3 and IL-5 prime normal human eosinophils to produce leukotriene C4 in response to soluble agonists. J Immunol. 1991 Dec 1;147(11):3855–3861. [PubMed] [Google Scholar]
- Tsai M., Shih L. S., Newlands G. F., Takeishi T., Langley K. E., Zsebo K. M., Miller H. R., Geissler E. N., Galli S. J. The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo. Analysis by anatomical distribution, histochemistry, and protease phenotype. J Exp Med. 1991 Jul 1;174(1):125–131. doi: 10.1084/jem.174.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valent P., Besemer J., Sillaber C., Butterfield J. H., Eher R., Majdic O., Kishi K., Klepetko W., Eckersberger F., Lechner K. Failure to detect IL-3-binding sites on human mast cells. J Immunol. 1990 Nov 15;145(10):3432–3437. [PubMed] [Google Scholar]
- Wasserman S. I. Mast cell biology. J Allergy Clin Immunol. 1990 Oct;86(4 Pt 2):590–593. doi: 10.1016/s0091-6749(05)80221-0. [DOI] [PubMed] [Google Scholar]
- Witte O. N. Steel locus defines new multipotent growth factor. Cell. 1990 Oct 5;63(1):5–6. doi: 10.1016/0092-8674(90)90280-r. [DOI] [PubMed] [Google Scholar]
- Wodnar-Filipowicz A., Heusser C. H., Moroni C. Production of the haemopoietic growth factors GM-CSF and interleukin-3 by mast cells in response to IgE receptor-mediated activation. Nature. 1989 May 11;339(6220):150–152. doi: 10.1038/339150a0. [DOI] [PubMed] [Google Scholar]
- Yarden Y., Kuang W. J., Yang-Feng T., Coussens L., Munemitsu S., Dull T. J., Chen E., Schlessinger J., Francke U., Ullrich A. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341–3351. doi: 10.1002/j.1460-2075.1987.tb02655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]