Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Feb;87(2):279–286. doi: 10.1111/j.1365-2249.1992.tb02988.x

Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis.

D A Hughes 1, P J Townsend 1, P L Haslam 1
PMCID: PMC1554263  PMID: 1370928

Abstract

Extrinsic allergic alveolitis (EAA) (synonym: hypersensitivity pneumonitis) is a hypersensitivity lung disease characterized by lymphocytic infiltrates in the pulmonary interstitial tissues. We have previously reported that the numbers of lymphocytes in bronchoalveolar lavage (BAL) samples in this disease correlate with levels of cholesterol and neutral lipid-laden 'foamy' macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which are known to be essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesterol is capable of enhancing the antigen-presenting function of mononuclear phagocytes by modulating the expression of HLA-D region products. Incubation of purified monocytes from healthy volunteers with cholesterol in serum-free medium induced a significant increase in both the percentages of monocytes expressing HLA-DQ (P less than 0.02) and in the intensity of expression of the three HLA-D sub-region products, HLA-DQ, -DP and -DR (P less than 0.02, less than 0.01, less than 0.05, respectively). The cholesterol pre-incubated monocytes also exhibited enhanced antigen-presenting function (P less than 0.05), compared with controls pre-incubated without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augment antigen presentation by modulating the expression of HLA-D region products on antigen-presenting cells. Apart from EAA, this observation may also have relevance to inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur in association with hypercholesterolaemia.

Full text

PDF
279

Selected References

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

  1. Aqel N. M., Ball R. Y., Waldmann H., Mitchinson M. J. Monocytic origin of foam cells in human atherosclerotic plaques. Atherosclerosis. 1984 Dec;53(3):265–271. doi: 10.1016/0021-9150(84)90127-8. [DOI] [PubMed] [Google Scholar]
  2. Ballance C. A. Ligation of the Innominate Artery for Subclavian Aneurysm. Proc R Soc Med. 1912;5(CLIN):99–104. doi: 10.1177/003591571200500236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brooks C. F., Moore M. Differential MHC class II expression on human peripheral blood monocytes and dendritic cells. Immunology. 1988 Feb;63(2):303–311. [PMC free article] [PubMed] [Google Scholar]
  4. Campbell D. A., du Bois R. M., Butcher R. G., Poulter L. W. The density of HLA-DR antigen expression on alveolar macrophages is increased in pulmonary sarcoidosis. Clin Exp Immunol. 1986 Jul;65(1):165–171. [PMC free article] [PubMed] [Google Scholar]
  5. Eckels D. D., Woody J. N., Hartzman R. J. Monoclonal and xenoantibodies specific for HLA-DR inhibit primary responses to HLA-D but fail to inhibit secondary proliferative (PLT) responses to allogeneic cells. Hum Immunol. 1981 Oct;3(2):133–142. doi: 10.1016/0198-8859(81)90050-1. [DOI] [PubMed] [Google Scholar]
  6. Emeson E. E., Robertson A. L., Jr T lymphocytes in aortic and coronary intimas. Their potential role in atherogenesis. Am J Pathol. 1988 Feb;130(2):369–376. [PMC free article] [PubMed] [Google Scholar]
  7. Fink J. N. Hypersensitivity pneumonitis. J Allergy Clin Immunol. 1984 Jul;74(1):1–10. doi: 10.1016/0091-6749(84)90077-0. [DOI] [PubMed] [Google Scholar]
  8. Hance A. J., Douches S., Winchester R. J., Ferrans V. J., Crystal R. G. Characterization of mononuclear phagocyte subpopulations in the human lung by using monoclonal antibodies: changes in alveolar macrophage phenotype associated with pulmonary sarcoidosis. J Immunol. 1985 Jan;134(1):284–292. [PubMed] [Google Scholar]
  9. Hansson G. K., Holm J., Jonasson L. Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol. 1989 Jul;135(1):169–175. [PMC free article] [PubMed] [Google Scholar]
  10. Hansson G. K., Jonasson L., Seifert P. S., Stemme S. Immune mechanisms in atherosclerosis. Arteriosclerosis. 1989 Sep-Oct;9(5):567–578. doi: 10.1161/01.atv.9.5.567. [DOI] [PubMed] [Google Scholar]
  11. Haslam P. L., Parker D. J., Townsend P. J. Increases in HLA-DQ, DP, DR, and transferrin receptors on alveolar macrophages in sarcoidosis and allergic alveolitis compared with fibrosing alveolitis. Chest. 1990 Mar;97(3):651–661. doi: 10.1378/chest.97.3.651. [DOI] [PubMed] [Google Scholar]
  12. Hoogsteden H. C., van Dongen J. J., van Hal P. T., Delahaye M., Hop W., Hilvering C. Phenotype of blood monocytes and alveolar macrophages in interstitial lung disease. Chest. 1989 Mar;95(3):574–577. doi: 10.1378/chest.95.3.574. [DOI] [PubMed] [Google Scholar]
  13. Hughes D. A., Haslam P. L. Effect of smoking on the lipid composition of lung lining fluid and relationship between immunostimulatory lipids, inflammatory cells and foamy macrophages in extrinsic allergic alveolitis. Eur Respir J. 1990 Nov;3(10):1128–1139. [PubMed] [Google Scholar]
  14. Ikeda M., Kodama H., Nohara N. Process of foam cell formation in diet-induced hypercholesterolemic rabbit and the Watanabe heritable hyperlipidemic rabbit. J Dermatol. 1987 Aug;14(4):305–312. doi: 10.1111/j.1346-8138.1987.tb03583.x. [DOI] [PubMed] [Google Scholar]
  15. Ip S. H., Abrahm J., Cooper R. A. Enhancement of blastogenesis in cholesterol-enriched lymphocytes. J Immunol. 1980 Jan;124(1):87–93. [PubMed] [Google Scholar]
  16. Jouanel P., Motta C., Brun J., Molina C., Dastugue B. Phospholipids and microviscosity study in broncho-alveolar lavage fluids from control subjects and from patients with extrinsic allergic alveolitis. Clin Chim Acta. 1981 Sep 10;115(2):211–221. doi: 10.1016/0009-8981(81)90077-2. [DOI] [PubMed] [Google Scholar]
  17. Klurfeld D. M. Identification of foam cells in human atherosclerotic lesions as macrophages using monoclonal antibodies. Arch Pathol Lab Med. 1985 May;109(5):445–449. [PubMed] [Google Scholar]
  18. Leatherman J. W., Michael A. F., Schwartz B. A., Hoidal J. R. Lung T cells in hypersensitivity pneumonitis. Ann Intern Med. 1984 Mar;100(3):390–392. doi: 10.7326/0003-4819-100-3-390. [DOI] [PubMed] [Google Scholar]
  19. Mornex J. F., Cordier G., Pages J., Vergnon J. M., Lefebvre R., Brune J., Revillard J. P. Activated lung lymphocytes in hypersensitivity pneumonitis. J Allergy Clin Immunol. 1984 Nov;74(5):719–727. doi: 10.1016/0091-6749(84)90236-7. [DOI] [PubMed] [Google Scholar]
  20. Muller C. P., Krueger G. R. Modulation of membrane proteins by vertical phase separation and membrane lipid fluidity. Basis for a new approach to tumor immunotherapy. Anticancer Res. 1986 Sep-Oct;6(5):1181–1193. [PubMed] [Google Scholar]
  21. Muller C. P., Stephany D. A., Shinitzky M., Wunderlich J. R. Changes in cell-surface expression of MHC and Thy-1.2 determinants following treatment with lipid modulating agents. J Immunol. 1983 Sep;131(3):1356–1362. [PubMed] [Google Scholar]
  22. Nunez G., Ball E. J., Stastny P. Antigen presentation by adherent cells from human peripheral blood. Correlation between T-cell activation and expression of HLA-DQ and -DR antigens. Hum Immunol. 1987 May;19(1):29–39. doi: 10.1016/0198-8859(87)90036-x. [DOI] [PubMed] [Google Scholar]
  23. Parker D. J., Haslam P. L. A new method to improve the discrimination between lymphocytes and contaminating erythrocytes in flow cytometric analytical techniques. J Immunol Methods. 1988 May 25;110(1):37–45. doi: 10.1016/0022-1759(88)90080-4. [DOI] [PubMed] [Google Scholar]
  24. Recalde H. R. A simple method of obtaining monocytes in suspension. J Immunol Methods. 1984 Apr 13;69(1):71–77. doi: 10.1016/0022-1759(84)90278-3. [DOI] [PubMed] [Google Scholar]
  25. Rennard S. I., Basset G., Lecossier D., O'Donnell K. M., Pinkston P., Martin P. G., Crystal R. G. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol (1985) 1986 Feb;60(2):532–538. doi: 10.1152/jappl.1986.60.2.532. [DOI] [PubMed] [Google Scholar]
  26. Reynolds H. Y., Fulmer J. D., Kazmierowski J. A., Roberts W. C., Frank M. M., Crystal R. G. Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. J Clin Invest. 1977 Jan;59(1):165–175. doi: 10.1172/JCI108615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sasazuki T., Matsushita S. MHC-linked immune suppression genes determine the phenotype of immune response to some natural antigens in humans. J Immunogenet. 1987 Apr-Jun;14(2-3):99–101. doi: 10.1111/j.1744-313x.1987.tb00368.x. [DOI] [PubMed] [Google Scholar]
  28. Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]
  29. Winston D. J., Territo M. C., Ho W. G., Miller M. J., Gale R. P., Golde D. W. Alveolar macrophage dysfunction in human bone marrow transplant recipients. Am J Med. 1982 Dec;73(6):859–866. doi: 10.1016/0002-9343(82)90777-x. [DOI] [PubMed] [Google Scholar]
  30. van oud Alblas A. B., van Furth R. Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state. J Exp Med. 1979 Jun 1;149(6):1504–1518. doi: 10.1084/jem.149.6.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES