Abstract
The aim of this study was to examine the role of lymphocytes in regulating expression of the 5-lipoxygenase pathway in monocytes. When monocytes were cultured over a period of days with lymphocytes, calcium ionophore-stimulated 5-lipoxygenase activity was enhanced. If lymphocytes alone were activated with lectins and their supernatants added to monocytes, stimulated 5-lipoxygenase activity was increased, whereas supernatants from lymphocytes cultured without lectins had no effect. Increased immunoreactive protein and mRNA for 5-lipoxygenase and 5-lipoxygenase activating protein were present in cells conditioned with lectin-activated lymphocyte supernatants. The effect of activated-lymphocyte supernatants could be mimicked by either GM-CSF or IL-3, but there was no additive effect with both cytokines. Both GM-CSF and IL-3 were present in the supernatant from lectin-activated lymphocytes at concentrations above their ED50, but were undetectable in the supernatant from nonactivated lymphocytes. The effect of lectin-activated lymphocyte supernatant could be inhibited by neutralizing antibodies to both cytokines, but not to either cytokine alone. We conclude that lymphocytes can regulate the expression of 5-lipoxygenase in monocytes, over a period of days, via the release of soluble factors, primarily GM-CSF and IL-3.
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- Bennett C. F., Chiang M. Y., Monia B. P., Crooke S. T. Regulation of 5-lipoxygenase and 5-lipoxygenase-activating protein expression in HL-60 cells. Biochem J. 1993 Jan 1;289(Pt 1):33–39. doi: 10.1042/bj2890033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bigby T. D., Holtzman M. J. Enhanced 5-lipoxygenase activity in lung macrophages compared to monocytes from normal subjects. J Immunol. 1987 Mar 1;138(5):1546–1550. [PubMed] [Google Scholar]
- Bigby T. D., Meslier N. Transcellular lipoxygenase metabolism between monocytes and platelets. J Immunol. 1989 Sep 15;143(6):1948–1954. [PubMed] [Google Scholar]
- Bonifati C., Carducci M., Cordiali Fei P., Trento E., Sacerdoti G., Fazio M., Ameglio F. Correlated increases of tumour necrosis factor-alpha, interleukin-6 and granulocyte monocyte-colony stimulating factor levels in suction blister fluids and sera of psoriatic patients--relationships with disease severity. Clin Exp Dermatol. 1994 Sep;19(5):383–387. doi: 10.1111/j.1365-2230.1994.tb02687.x. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Broide D. H., Lotz M., Cuomo A. J., Coburn D. A., Federman E. C., Wasserman S. I. Cytokines in symptomatic asthma airways. J Allergy Clin Immunol. 1992 May;89(5):958–967. doi: 10.1016/0091-6749(92)90218-q. [DOI] [PubMed] [Google Scholar]
- Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
- Coffey M. J., Wilcoxen S. E., Peters-Golden M. Increases in 5-lipoxygenase activating protein expression account for enhanced capacity for 5-lipoxygenase metabolism that accompanies differentiation of peripheral blood monocytes into alveolar macrophages. Am J Respir Cell Mol Biol. 1994 Aug;11(2):153–158. doi: 10.1165/ajrcmb.11.2.8049076. [DOI] [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]
- Dimri R., Nissimov L., Keisari Y. Effect of human recombinant granulocyte-macrophage colony-stimulating factor and IL-3 on the expression of surface markers of human monocyte-derived macrophages in long-term cultures. Lymphokine Cytokine Res. 1994 Aug;13(4):239–245. [PubMed] [Google Scholar]
- Elliott M. J., Vadas M. A., Cleland L. G., Gamble J. R., Lopez A. F. IL-3 and granulocyte-macrophage colony-stimulating factor stimulate two distinct phases of adhesion in human monocytes. J Immunol. 1990 Jul 1;145(1):167–176. [PubMed] [Google Scholar]
- Elliott M. J., Vadas M. A., Eglinton J. M., Park L. S., To L. B., Cleland L. G., Clark S. C., Lopez A. F. Recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor show common biological effects and binding characteristics on human monocytes. Blood. 1989 Nov 15;74(7):2349–2359. [PubMed] [Google Scholar]
- Fair A., Pritchard K. A., Jr Oxidized low density lipoprotein increases U937 cell 5-lipoxygenase activity: induction of 5-lipoxygenase activating protein. Biochem Biophys Res Commun. 1994 Jun 15;201(2):1014–1020. doi: 10.1006/bbrc.1994.1803. [DOI] [PubMed] [Google Scholar]
- Hoshiko S., Rådmark O., Samuelsson B. Characterization of the human 5-lipoxygenase gene promoter. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9073–9077. doi: 10.1073/pnas.87.23.9073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jakobsson P. J., Odlander B., Claesson H. E. Effects of monocyte-lymphocyte interaction on the synthesis of leukotriene B4. Eur J Biochem. 1991 Mar 14;196(2):395–400. doi: 10.1111/j.1432-1033.1991.tb15829.x. [DOI] [PubMed] [Google Scholar]
- Kay A. B., Ying S., Varney V., Gaga M., Durham S. R., Moqbel R., Wardlaw A. J., Hamid Q. Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects. J Exp Med. 1991 Mar 1;173(3):775–778. doi: 10.1084/jem.173.3.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kennedy B. P., Diehl R. E., Boie Y., Adam M., Dixon R. A. Gene characterization and promoter analysis of the human 5-lipoxygenase-activating protein (FLAP). J Biol Chem. 1991 May 5;266(13):8511–8516. [PubMed] [Google Scholar]
- Krump E., Borgeat P. Kinetics of 5-lipoxygenase activation, arachidonic acid release, and leukotriene synthesis in human neutrophils: effects of granulocyte-macrophage colony-stimulating factor. Biochim Biophys Acta. 1994 Jul 14;1213(2):135–139. doi: 10.1016/0005-2760(94)90019-1. [DOI] [PubMed] [Google Scholar]
- Lawrence D. A. Identification and activation of latent transforming growth factor beta. Methods Enzymol. 1991;198:327–336. doi: 10.1016/0076-6879(91)98033-3. [DOI] [PubMed] [Google Scholar]
- Lewis R. A., Austen K. F., Soberman R. J. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med. 1990 Sep 6;323(10):645–655. doi: 10.1056/NEJM199009063231006. [DOI] [PubMed] [Google Scholar]
- Lopez A. F., Elliott M. J., Woodcock J., Vadas M. A. GM-CSF, IL-3 and IL-5: cross-competition on human haemopoietic cells. Immunol Today. 1992 Dec;13(12):495–500. doi: 10.1016/0167-5699(92)90025-3. [DOI] [PubMed] [Google Scholar]
- Marini M., Avoni E., Hollemborg J., Mattoli S. Cytokine mRNA profile and cell activation in bronchoalveolar lavage fluid from nonatopic patients with symptomatic asthma. Chest. 1992 Sep;102(3):661–669. doi: 10.1378/chest.102.3.661. [DOI] [PubMed] [Google Scholar]
- Massey W., Friedman B., Kato M., Cooper P., Kagey-Sobotka A., Lichtenstein L. M., Schleimer R. P. Appearance of granulocyte-macrophage colony-stimulating factor activity at allergen-challenged cutaneous late-phase reaction sites. J Immunol. 1993 Feb 1;150(3):1084–1092. [PubMed] [Google Scholar]
- McDonald P. P., Pouliot M., Borgeat P., McColl S. R. Induction by chemokines of lipid mediator synthesis in granulocyte-macrophage colony-stimulating factor-treated human neutrophils. J Immunol. 1993 Dec 1;151(11):6399–6409. [PubMed] [Google Scholar]
- Meslier N., Aldrich A. J., Bigby T. D. Effect of interferon-gamma on the 5-lipoxygenase pathway of rat lung macrophages. Am J Respir Cell Mol Biol. 1992 Jan;6(1):93–99. doi: 10.1165/ajrcmb/6.1.93. [DOI] [PubMed] [Google Scholar]
- Miyajima A., Mui A. L., Ogorochi T., Sakamaki K. Receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5. Blood. 1993 Oct 1;82(7):1960–1974. [PubMed] [Google Scholar]
- Munafo D. A., Shindo K., Baker J. R., Bigby T. D. Leukotriene A4 hydrolase in human bronchoalveolar lavage fluid. J Clin Invest. 1994 Mar;93(3):1042–1050. doi: 10.1172/JCI117053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Owen W. F., Jr, Rothenberg M. E., Silberstein D. S., Gasson J. C., Stevens R. L., Austen K. F., Soberman R. J. Regulation of human eosinophil viability, density, and function by granulocyte/macrophage colony-stimulating factor in the presence of 3T3 fibroblasts. J Exp Med. 1987 Jul 1;166(1):129–141. doi: 10.1084/jem.166.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palmantier R., Surette M. E., Sanchez A., Braquet P., Borgeat P. Priming for the synthesis of 5-lipoxygenase products in human blood ex vivo by human granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. Lab Invest. 1994 May;70(5):696–704. [PubMed] [Google Scholar]
- Peters-Golden M., McNish R. W. Redistribution of 5-lipoxygenase and cytosolic phospholipase A2 to the nuclear fraction upon macrophage activation. Biochem Biophys Res Commun. 1993 Oct 15;196(1):147–153. doi: 10.1006/bbrc.1993.2227. [DOI] [PubMed] [Google Scholar]
- Piechele G., Colli S., Tremoli E., Maggi A. 5-Lipoxygenase gene expression in HL60 cells during differentiation with DMSO. Pharmacol Res. 1993 Jan-Feb;27(1):53–60. doi: 10.1006/phrs.1993.1005. [DOI] [PubMed] [Google Scholar]
- Pouliot M., McDonald P. P., Borgeat P., McColl S. R. Granulocyte/macrophage colony-stimulating factor stimulates the expression of the 5-lipoxygenase-activating protein (FLAP) in human neutrophils. J Exp Med. 1994 Apr 1;179(4):1225–1232. doi: 10.1084/jem.179.4.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pouliot M., McDonald P. P., Khamzina L., Borgeat P., McColl S. R. Granulocyte-macrophage colony-stimulating factor enhances 5-lipoxygenase levels in human polymorphonuclear leukocytes. J Immunol. 1994 Jan 15;152(2):851–858. [PubMed] [Google Scholar]
- Pueringer R. J., Bahns C. C., Hunninghake G. W. Alveolar macrophages have greater amounts of the enzyme 5-lipoxygenase than do monocytes. J Appl Physiol (1985) 1992 Aug;73(2):781–786. doi: 10.1152/jappl.1992.73.2.781. [DOI] [PubMed] [Google Scholar]
- Robin G., Markovich S., Athamna A., Keisari Y. Human recombinant granulocyte-macrophage colony-stimulating factor augments viability and cytotoxic activities of human monocyte-derived macrophages in long-term cultures. Lymphokine Cytokine Res. 1991 Aug;10(4):257–263. [PubMed] [Google Scholar]
- Rothenberg M. E., Owen W. F., Jr, Silberstein D. S., Woods J., Soberman R. J., Austen K. F., Stevens R. L. Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human interleukin 3. J Clin Invest. 1988 Jun;81(6):1986–1992. doi: 10.1172/JCI113547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roubin R., Elsas P. P., Fiers W., Dessein A. J. Recombinant human tumour necrosis factor (rTNF)2 enhances leukotriene biosynthesis in neutrophils and eosinophils stimulated with the Ca2+ ionophore A23187. Clin Exp Immunol. 1987 Nov;70(2):484–490. [PMC free article] [PubMed] [Google Scholar]
- Samuelsson B., Dahlén S. E., Lindgren J. A., Rouzer C. A., Serhan C. N. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987 Sep 4;237(4819):1171–1176. doi: 10.1126/science.2820055. [DOI] [PubMed] [Google Scholar]
- Samuelsson B., Hoshiko S., Rådmark O. Characterization of the promoter of the human 5-lipoxygenase gene. Adv Prostaglandin Thromboxane Leukot Res. 1991;21A:1–8. [PubMed] [Google Scholar]
- Schatz-Munding M., Ullrich V. Priming of human polymorphonuclear leukocytes with granulocyte-macrophage colony-stimulating factor involves protein kinase C rather than enhanced calcium mobilisation. Eur J Biochem. 1992 Mar 1;204(2):705–712. doi: 10.1111/j.1432-1033.1992.tb16685.x. [DOI] [PubMed] [Google Scholar]
- Shannon M. F., Himes S. R., Coles L. S. GM-CSF and IL-2 share common control mechanisms in response to costimulatory signals in T cells. J Leukoc Biol. 1995 May;57(5):767–773. doi: 10.1002/jlb.57.5.767. [DOI] [PubMed] [Google Scholar]
- Silberstein D. S., Owen W. F., Gasson J. C., DiPersio J. F., Golde D. W., Bina J. C., Soberman R., Austen K. F., David J. R. Enhancement of human eosinophil cytotoxicity and leukotriene synthesis by biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor. J Immunol. 1986 Nov 15;137(10):3290–3294. [PubMed] [Google Scholar]
- Stanková J., Rola-Pleszczynski M., Dubois C. M. Granulocyte-macrophage colony-stimulating factor increases 5-lipoxygenase gene transcription and protein expression in human neutrophils. Blood. 1995 Jun 15;85(12):3719–3726. [PubMed] [Google Scholar]
- Steinhilber D., Rådmark O., Samuelsson B. Transforming growth factor beta upregulates 5-lipoxygenase activity during myeloid cell maturation. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5984–5988. doi: 10.1073/pnas.90.13.5984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Surette M. E., Palmantier R., Gosselin J., Borgeat P. Lipopolysaccharides prime whole human blood and isolated neutrophils for the increased synthesis of 5-lipoxygenase products by enhancing arachidonic acid availability: involvement of the CD14 antigen. J Exp Med. 1993 Oct 1;178(4):1347–1355. doi: 10.1084/jem.178.4.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vitetta E. S., Fernandez-Botran R., Myers C. D., Sanders V. M. Cellular interactions in the humoral immune response. Adv Immunol. 1989;45:1–105. doi: 10.1016/s0065-2776(08)60692-6. [DOI] [PubMed] [Google Scholar]
- Walker C., Bauer W., Braun R. K., Menz G., Braun P., Schwarz F., Hansel T. T., Villiger B. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med. 1994 Oct;150(4):1038–1048. doi: 10.1164/ajrccm.150.4.7921434. [DOI] [PubMed] [Google Scholar]
- Woods J. W., Evans J. F., Ethier D., Scott S., Vickers P. J., Hearn L., Heibein J. A., Charleson S., Singer I. I. 5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes. J Exp Med. 1993 Dec 1;178(6):1935–1946. doi: 10.1084/jem.178.6.1935. [DOI] [PMC free article] [PubMed] [Google Scholar]