Abstract
By in situ hybridization, 44-100% of the blood eosinophils from five patients with hypereosinophilia and four normal subjects exhibited intense hybridization signals for TNF-alpha mRNA. TNF-alpha protein was detectable by immunohistochemistry in blood eosinophils of hypereosinophilic subjects, and purified blood eosinophils from three atopic donors exhibited cycloheximide-inhibitable spontaneous release of TNF-alpha in vitro. Many blood eosinophils (39-91%) from hypereosinophilic donors exhibited intense labeling for macrophage inflammatory protein-1 alpha (MIP-1 alpha) mRNA, whereas eosinophils of normal donors demonstrated only weak or undetectable hybridization signals for MIP-1 alpha mRNA. Most tissue eosinophils infiltrating nasal polyps were strongly positive for both TNF-alpha and MIP-1 alpha mRNA. By Northern blot analysis, highly enriched blood eosinophils from a patient with the idiopathic hypereosinophilic syndrome exhibited differential expression of TNF-alpha and MIP-1 alpha mRNA. These findings indicate that human eosinophils represent a potential source of TNF-alpha and MIP-1 alpha, that levels of expression of mRNA for both cytokines are high in the blood eosinophils of hypereosinophilic donors and in eosinophils infiltrating nasal polyps, that the eosinophils of normal subjects express higher levels of TNF-alpha than MIP-1 alpha mRNA, and that eosinophils purified from the blood of atopic donors can release TNF-alpha in vitro.
Full text
PDF











Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amiri P., Locksley R. M., Parslow T. G., Sadick M., Rector E., Ritter D., McKerrow J. H. Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature. 1992 Apr 16;356(6370):604–607. doi: 10.1038/356604a0. [DOI] [PubMed] [Google Scholar]
- Benyon R. C., Bissonnette E. Y., Befus A. D. Tumor necrosis factor-alpha dependent cytotoxicity of human skin mast cells is enhanced by anti-IgE antibodies. J Immunol. 1991 Oct 1;147(7):2253–2258. [PubMed] [Google Scholar]
- Beutler B., Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625–655. doi: 10.1146/annurev.iy.07.040189.003205. [DOI] [PubMed] [Google Scholar]
- Bochner B. S., Luscinskas F. W., Gimbrone M. A., Jr, Newman W., Sterbinsky S. A., Derse-Anthony C. P., Klunk D., Schleimer R. P. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med. 1991 Jun 1;173(6):1553–1557. doi: 10.1084/jem.173.6.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bosma P. J., Kooistra T. Different induction of two plasminogen activator inhibitor 1 mRNA species by phorbol ester in human hepatoma cells. J Biol Chem. 1991 Sep 25;266(27):17845–17849. [PubMed] [Google Scholar]
- Bradley B. L., Azzawi M., Jacobson M., Assoufi B., Collins J. V., Irani A. M., Schwartz L. B., Durham S. R., Jeffery P. K., Kay A. B. Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. J Allergy Clin Immunol. 1991 Oct;88(4):661–674. doi: 10.1016/0091-6749(91)90160-p. [DOI] [PubMed] [Google Scholar]
- Broide D. H., Gleich G. J., Cuomo A. J., Coburn D. A., Federman E. C., Schwartz L. B., Wasserman S. I. Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway. J Allergy Clin Immunol. 1991 Oct;88(4):637–648. doi: 10.1016/0091-6749(91)90158-k. [DOI] [PubMed] [Google Scholar]
- Burd P. R., Rogers H. W., Gordon J. R., Martin C. A., Jayaraman S., Wilson S. D., Dvorak A. M., Galli S. J., Dorf M. E. Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines. J Exp Med. 1989 Jul 1;170(1):245–257. doi: 10.1084/jem.170.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Busse W. W., Sedgwick J. B. Eosinophils in asthma. Ann Allergy. 1992 Mar;68(3):286–290. [PubMed] [Google Scholar]
- Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
- Del Pozo V., De Andres B., Martin E., Maruri N., Zubeldia J. M., Palomino P., Lahoz C. Murine eosinophils and IL-1: alpha IL-1 mRNA detection by in situ hybridization. Production and release of IL-1 from peritoneal eosinophils. J Immunol. 1990 Apr 15;144(8):3117–3122. [PubMed] [Google Scholar]
- Desreumaux P., Janin A., Colombel J. F., Prin L., Plumas J., Emilie D., Torpier G., Capron A., Capron M. Interleukin 5 messenger RNA expression by eosinophils in the intestinal mucosa of patients with coeliac disease. J Exp Med. 1992 Jan 1;175(1):293–296. doi: 10.1084/jem.175.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Djeu J. Y., Serbousek D., Blanchard D. K. Release of tumor necrosis factor by human polymorphonuclear leukocytes. Blood. 1990 Oct 1;76(7):1405–1409. [PubMed] [Google Scholar]
- Dubravec D. B., Spriggs D. R., Mannick J. A., Rodrick M. L. Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6758–6761. doi: 10.1073/pnas.87.17.6758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dugaiczyk A., Haron J. A., Stone E. M., Dennison O. E., Rothblum K. N., Schwartz R. J. Cloning and sequencing of a deoxyribonucleic acid copy of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid isolated from chicken muscle. Biochemistry. 1983 Mar 29;22(7):1605–1613. doi: 10.1021/bi00276a013. [DOI] [PubMed] [Google Scholar]
- Elovic A., Galli S. J., Weller P. F., Chang A. L., Chiang T., Chou M. Y., Donoff R. B., Gallagher G. T., Matossian K., McBride J. Production of transforming growth factor alpha by hamster eosinophils. Am J Pathol. 1990 Dec;137(6):1425–1434. [PMC free article] [PubMed] [Google Scholar]
- Fahey T. J., 3rd, Tracey K. J., Tekamp-Olson P., Cousens L. S., Jones W. G., Shires G. T., Cerami A., Sherry B. Macrophage inflammatory protein 1 modulates macrophage function. J Immunol. 1992 May 1;148(9):2764–2769. [PubMed] [Google Scholar]
- Fauci A. S., Harley J. B., Roberts W. C., Ferrans V. J., Gralnick H. R., Bjornson B. H. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med. 1982 Jul;97(1):78–92. doi: 10.7326/0003-4819-97-1-78. [DOI] [PubMed] [Google Scholar]
- Galli S. J. New concepts about the mast cell. N Engl J Med. 1993 Jan 28;328(4):257–265. doi: 10.1056/NEJM199301283280408. [DOI] [PubMed] [Google Scholar]
- Gamble J. R., Harlan J. M., Klebanoff S. J., Vadas M. A. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8667–8671. doi: 10.1073/pnas.82.24.8667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gleich G. J., Adolphson C. R. The eosinophilic leukocyte: structure and function. Adv Immunol. 1986;39:177–253. doi: 10.1016/s0065-2776(08)60351-x. [DOI] [PubMed] [Google Scholar]
- Gordon J. R., Burd P. R., Galli S. J. Mast cells as a source of multifunctional cytokines. Immunol Today. 1990 Dec;11(12):458–464. doi: 10.1016/0167-5699(90)90176-a. [DOI] [PubMed] [Google Scholar]
- Gordon J. R., Galli S. J. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature. 1990 Jul 19;346(6281):274–276. doi: 10.1038/346274a0. [DOI] [PubMed] [Google Scholar]
- Gordon J. R., Galli S. J. Release of both preformed and newly synthesized tumor necrosis factor alpha (TNF-alpha)/cachectin by mouse mast cells stimulated via the Fc epsilon RI. A mechanism for the sustained action of mast cell-derived TNF-alpha during IgE-dependent biological responses. J Exp Med. 1991 Jul 1;174(1):103–107. doi: 10.1084/jem.174.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gosset P., Tsicopoulos A., Wallaert B., Vannimenus C., Joseph M., Tonnel A. B., Capron A. Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol. 1991 Oct;88(4):561–571. doi: 10.1016/0091-6749(91)90149-i. [DOI] [PubMed] [Google Scholar]
- Hamid Q., Barkans J., Meng Q., Ying S., Abrams J. S., Kay A. B., Moqbel R. Human eosinophils synthesize and secrete interleukin-6, in vitro. Blood. 1992 Sep 15;80(6):1496–1501. [PubMed] [Google Scholar]
- Hansel T. T., De Vries I. J., Iff T., Rihs S., Wandzilak M., Betz S., Blaser K., Walker C. An improved immunomagnetic procedure for the isolation of highly purified human blood eosinophils. J Immunol Methods. 1991 Dec 15;145(1-2):105–110. doi: 10.1016/0022-1759(91)90315-7. [DOI] [PubMed] [Google Scholar]
- Kips J. C., Tavernier J., Pauwels R. A. Tumor necrosis factor causes bronchial hyperresponsiveness in rats. Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):332–336. doi: 10.1164/ajrccm/145.2_Pt_1.332. [DOI] [PubMed] [Google Scholar]
- Kita H., Ohnishi T., Okubo Y., Weiler D., Abrams J. S., Gleich G. J. Granulocyte/macrophage colony-stimulating factor and interleukin 3 release from human peripheral blood eosinophils and neutrophils. J Exp Med. 1991 Sep 1;174(3):745–748. doi: 10.1084/jem.174.3.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kyan-Aung U., Haskard D. O., Poston R. N., Thornhill M. H., Lee T. H. Endothelial leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 mediate the adhesion of eosinophils to endothelial cells in vitro and are expressed by endothelium in allergic cutaneous inflammation in vivo. J Immunol. 1991 Jan 15;146(2):521–528. [PubMed] [Google Scholar]
- Leung D. Y., Pober J. S., Cotran R. S. Expression of endothelial-leukocyte adhesion molecule-1 in elicited late phase allergic reactions. J Clin Invest. 1991 May;87(5):1805–1809. doi: 10.1172/JCI115201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lucey D. R., Nicholson-Weller A., Weller P. F. Mature human eosinophils have the capacity to express HLA-DR. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1348–1351. doi: 10.1073/pnas.86.4.1348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCrone E. L., Lucey D. R., Weller P. F. Fluorescent staining for leukocyte chemotaxis. Eosinophil-specific fluorescence with aniline blue. J Immunol Methods. 1988 Nov 10;114(1-2):79–88. doi: 10.1016/0022-1759(88)90157-3. [DOI] [PubMed] [Google Scholar]
- Moqbel R., Hamid Q., Ying S., Barkans J., Hartnell A., Tsicopoulos A., Wardlaw A. J., Kay A. B. Expression of mRNA and immunoreactivity for the granulocyte/macrophage colony-stimulating factor in activated human eosinophils. J Exp Med. 1991 Sep 1;174(3):749–752. doi: 10.1084/jem.174.3.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohno I., Lea R. G., Flanders K. C., Clark D. A., Banwatt D., Dolovich J., Denburg J., Harley C. B., Gauldie J., Jordana M. Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). J Clin Invest. 1992 May;89(5):1662–1668. doi: 10.1172/JCI115764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oppenheim J. J., Zachariae C. O., Mukaida N., Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. doi: 10.1146/annurev.iy.09.040191.003153. [DOI] [PubMed] [Google Scholar]
- Pennica D., Nedwin G. E., Hayflick J. S., Seeburg P. H., Derynck R., Palladino M. A., Kohr W. J., Aggarwal B. B., Goeddel D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. doi: 10.1038/312724a0. [DOI] [PubMed] [Google Scholar]
- Saukkonen K., Sande S., Cioffe C., Wolpe S., Sherry B., Cerami A., Tuomanen E. The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. J Exp Med. 1990 Feb 1;171(2):439–448. doi: 10.1084/jem.171.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Silberstein D. S., David J. R. Tumor necrosis factor enhances eosinophil toxicity to Schistosoma mansoni larvae. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1055–1059. doi: 10.1073/pnas.83.4.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tepper R. I., Coffman R. L., Leder P. An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science. 1992 Jul 24;257(5069):548–551. doi: 10.1126/science.1636093. [DOI] [PubMed] [Google Scholar]
- Walsh L. J., Trinchieri G., Waldorf H. A., Whitaker D., Murphy G. F. Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4220–4224. doi: 10.1073/pnas.88.10.4220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weller P. F., Rand T. H., Barrett T., Elovic A., Wong D. T., Finberg R. W. Accessory cell function of human eosinophils. HLA-DR-dependent, MHC-restricted antigen-presentation and IL-1 alpha expression. J Immunol. 1993 Mar 15;150(6):2554–2562. [PubMed] [Google Scholar]
- Weller P. F., Rand T. H., Goelz S. E., Chi-Rosso G., Lobb R. R. Human eosinophil adherence to vascular endothelium mediated by binding to vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7430–7433. doi: 10.1073/pnas.88.16.7430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weller P. F. The immunobiology of eosinophils. N Engl J Med. 1991 Apr 18;324(16):1110–1118. doi: 10.1056/NEJM199104183241607. [DOI] [PubMed] [Google Scholar]
- Wershil B. K., Wang Z. S., Gordon J. R., Galli S. J. Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-alpha. J Clin Invest. 1991 Feb;87(2):446–453. doi: 10.1172/JCI115016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolpe S. D., Cerami A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 1989 Dec;3(14):2565–2573. doi: 10.1096/fasebj.3.14.2687068. [DOI] [PubMed] [Google Scholar]
- Wolpe S. D., Davatelis G., Sherry B., Beutler B., Hesse D. G., Nguyen H. T., Moldawer L. L., Nathan C. F., Lowry S. F., Cerami A. Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties. J Exp Med. 1988 Feb 1;167(2):570–581. doi: 10.1084/jem.167.2.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong D. T., Elovic A., Matossian K., Nagura N., McBride J., Chou M. Y., Gordon J. R., Rand T. H., Galli S. J., Weller P. F. Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1. Blood. 1991 Nov 15;78(10):2702–2707. [PubMed] [Google Scholar]
- Wong D. T., Weller P. F., Galli S. J., Elovic A., Rand T. H., Gallagher G. T., Chiang T., Chou M. Y., Matossian K., McBride J. Human eosinophils express transforming growth factor alpha. J Exp Med. 1990 Sep 1;172(3):673–681. doi: 10.1084/jem.172.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ying S., Robinson D. S., Varney V., Meng Q., Tsicopoulos A., Moqbel R., Durham S. R., Kay A. B., Hamid Q. TNF alpha mRNA expression in allergic inflammation. Clin Exp Allergy. 1991 Nov;21(6):745–750. doi: 10.1111/j.1365-2222.1991.tb03205.x. [DOI] [PubMed] [Google Scholar]