PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
 
J Clin Invest. 1993 June; 91(6): 2673–2684.
PMCID: PMC443331

Human eosinophils can express the cytokines tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha.

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

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (4.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Weller PF. The immunobiology of eosinophils. N Engl J Med. 1991 Apr 18;324(16):1110–1118. [PubMed]
  • Gleich GJ, Adolphson CR. The eosinophilic leukocyte: structure and function. Adv Immunol. 1986;39:177–253. [PubMed]
  • Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, Bjornson BH. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med. 1982 Jul;97(1):78–92. [PubMed]
  • Del Pozo V, De Andres B, Martin E, Maruri N, Zubeldia JM, 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]
  • Wong DT, Weller PF, Galli SJ, Elovic A, Rand TH, Gallagher GT, Chiang T, Chou MY, Matossian K, McBride J, et al. Human eosinophils express transforming growth factor alpha. J Exp Med. 1990 Sep 1;172(3):673–681. [PMC free article] [PubMed]
  • Elovic A, Galli SJ, Weller PF, Chang AL, Chiang T, Chou MY, Donoff RB, Gallagher GT, Matossian K, McBride J, et al. Production of transforming growth factor alpha by hamster eosinophils. Am J Pathol. 1990 Dec;137(6):1425–1434. [PubMed]
  • Wong DT, Elovic A, Matossian K, Nagura N, McBride J, Chou MY, Gordon JR, Rand TH, Galli SJ, Weller PF. Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1. Blood. 1991 Nov 15;78(10):2702–2707. [PubMed]
  • Ohno I, Lea RG, Flanders KC, Clark DA, Banwatt D, Dolovich J, Denburg J, Harley CB, 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. [PMC free article] [PubMed]
  • Moqbel R, Hamid Q, Ying S, Barkans J, Hartnell A, Tsicopoulos A, Wardlaw AJ, Kay AB. 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. [PMC free article] [PubMed]
  • Kita H, Ohnishi T, Okubo Y, Weiler D, Abrams JS, Gleich GJ. 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. [PMC free article] [PubMed]
  • Desreumaux P, Janin A, Colombel JF, 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. [PMC free article] [PubMed]
  • Weller PF, Rand TH, Barrett T, Elovic A, Wong DT, Finberg RW. 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]
  • Hamid Q, Barkans J, Meng Q, Ying S, Abrams JS, Kay AB, Moqbel R. Human eosinophils synthesize and secrete interleukin-6, in vitro. Blood. 1992 Sep 15;80(6):1496–1501. [PubMed]
  • Gordon JR, Galli SJ. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature. 1990 Jul 19;346(6281):274–276. [PubMed]
  • Gordon JR, Galli SJ. 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. [PMC free article] [PubMed]
  • Wershil BK, Wang ZS, Gordon JR, Galli SJ. 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. [PMC free article] [PubMed]
  • Walsh LJ, Trinchieri G, Waldorf HA, Whitaker D, Murphy GF. 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. [PubMed]
  • Leung DY, Pober JS, Cotran RS. Expression of endothelial-leukocyte adhesion molecule-1 in elicited late phase allergic reactions. J Clin Invest. 1991 May;87(5):1805–1809. [PMC free article] [PubMed]
  • Ying S, Robinson DS, Varney V, Meng Q, Tsicopoulos A, Moqbel R, Durham SR, Kay AB, Hamid Q. TNF alpha mRNA expression in allergic inflammation. Clin Exp Allergy. 1991 Nov;21(6):745–750. [PubMed]
  • Gosset P, Tsicopoulos A, Wallaert B, Vannimenus C, Joseph M, Tonnel AB, 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. [PubMed]
  • Gordon JR, Burd PR, Galli SJ. Mast cells as a source of multifunctional cytokines. Immunol Today. 1990 Dec;11(12):458–464. [PubMed]
  • Fahey TJ, 3rd, Tracey KJ, Tekamp-Olson P, Cousens LS, Jones WG, Shires GT, Cerami A, Sherry B. Macrophage inflammatory protein 1 modulates macrophage function. J Immunol. 1992 May 1;148(9):2764–2769. [PubMed]
  • Lucey DR, Nicholson-Weller A, Weller PF. Mature human eosinophils have the capacity to express HLA-DR. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1348–1351. [PubMed]
  • Collins SJ, Gallo RC, Gallagher RE. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. [PubMed]
  • Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. [PubMed]
  • Burd PR, Rogers HW, Gordon JR, Martin CA, Jayaraman S, Wilson SD, Dvorak AM, Galli SJ, Dorf ME. 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. [PMC free article] [PubMed]
  • Dugaiczyk A, Haron JA, Stone EM, Dennison OE, Rothblum KN, Schwartz RJ. 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. [PubMed]
  • McCrone EL, Lucey DR, Weller PF. Fluorescent staining for leukocyte chemotaxis. Eosinophil-specific fluorescence with aniline blue. J Immunol Methods. 1988 Nov 10;114(1-2):79–88. [PubMed]
  • Hansel TT, De Vries IJ, 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. [PubMed]
  • Djeu JY, Serbousek D, Blanchard DK. Release of tumor necrosis factor by human polymorphonuclear leukocytes. Blood. 1990 Oct 1;76(7):1405–1409. [PubMed]
  • Dubravec DB, Spriggs DR, Mannick JA, Rodrick ML. 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. [PubMed]
  • Bosma PJ, 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]
  • Gamble JR, Harlan JM, Klebanoff SJ, Vadas MA. 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. [PubMed]
  • Beutler B, Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625–655. [PubMed]
  • Wolpe SD, Cerami A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 1989 Dec;3(14):2565–2573. [PubMed]
  • Oppenheim JJ, Zachariae CO, Mukaida N, Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. [PubMed]
  • Wolpe SD, Davatelis G, Sherry B, Beutler B, Hesse DG, Nguyen HT, Moldawer LL, Nathan CF, Lowry SF, 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Kyan-Aung U, Haskard DO, Poston RN, Thornhill MH, Lee TH. 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]
  • Weller PF, Rand TH, Goelz SE, Chi-Rosso G, Lobb RR. 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. [PubMed]
  • Bochner BS, Luscinskas FW, Gimbrone MA, Jr, Newman W, Sterbinsky SA, Derse-Anthony CP, Klunk D, Schleimer RP. 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. [PMC free article] [PubMed]
  • Benyon RC, Bissonnette EY, Befus AD. 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]
  • Galli SJ. New concepts about the mast cell. N Engl J Med. 1993 Jan 28;328(4):257–265. [PubMed]
  • Silberstein DS, David JR. Tumor necrosis factor enhances eosinophil toxicity to Schistosoma mansoni larvae. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1055–1059. [PubMed]
  • Amiri P, Locksley RM, Parslow TG, Sadick M, Rector E, Ritter D, McKerrow JH. Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature. 1992 Apr 16;356(6370):604–607. [PubMed]
  • Tepper RI, Coffman RL, Leder P. An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science. 1992 Jul 24;257(5069):548–551. [PubMed]
  • Bradley BL, Azzawi M, Jacobson M, Assoufi B, Collins JV, Irani AM, Schwartz LB, Durham SR, Jeffery PK, Kay AB. 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. [PubMed]
  • Broide DH, Gleich GJ, Cuomo AJ, Coburn DA, Federman EC, Schwartz LB, Wasserman SI. Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway. J Allergy Clin Immunol. 1991 Oct;88(4):637–648. [PubMed]
  • Kips JC, Tavernier J, Pauwels RA. Tumor necrosis factor causes bronchial hyperresponsiveness in rats. Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):332–336. [PubMed]
  • Busse WW, Sedgwick JB. Eosinophils in asthma. Ann Allergy. 1992 Mar;68(3):286–290. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation