Home LiteratureArticle Details
PMID: 3486887 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals.

The Journal of clinical investigation ·Vol. 77 ·No. 6 ·1986-06-00 ·Pages 1952-61

Mornex JF, Chytil-Weir A, Martinet Y, Courtney M, LeCocq JP, Crystal RG

Abstract

To evaluate the contribution of mononuclear phagocytes, and particularly alveolar macrophages, to alpha-1-antitrypsin (alpha 1AT) production in normal and alpha 1AT-deficient individuals, Northern analysis with a human alpha 1AT complementary DNA was used to demonstrate that alpha 1AT messenger RNA (mRNA) can be detected in liver, blood monocytes, and alveolar macrophages. Quantification of alpha 1AT mRNA expression demonstrated that: (a) type PiMM monocytes and alveolar macrophages expressed, respectively, 200-fold and 70-fold less alpha 1AT mRNA per cell than the liver; (b) the level of expression of the alpha 1AT gene was increased during the in vitro maturation of blood monocytes; and (c) blood monocyte and alveolar macrophage levels of expression of the alpha 1AT gene were the same in PiMM and PiZZ individuals. However, the amount of newly synthesized alpha 1AT secreted by ZZ alveolar macrophages was 10 times lower than that secreted by MM alveolar macrophages. Thus, mononuclear phagocytes of PiZZ individuals express a secretory defect in alpha 1AT in a fashion similar to hepatocytes. Not only do mononuclear phagocytes provide a readily accessible cell to evaluate the regulation of alpha 1AT gene expression, but these cells may contribute to the levels of alpha 1AT present in the lower respiratory tract in the normal and ZZ states.

MeSH Terms
Adult DNA/analysis Female Gene Expression Regulation Humans Liver/metabolism Male Methionine/metabolism Middle Aged Phagocytes/metabolism Phenotype Pulmonary Alveoli/cytology RNA, Messenger/analysis Smoking alpha 1-Antitrypsin/genetics
Chemicals
RNA, Messenger alpha 1-Antitrypsin DNA Methionine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Mornex J F
Chytil-Weir A
Martinet Y
Courtney M
LeCocq J P
Crystal R G
References (90)
90 references, click to expand
  1. Macrophage maturation: differences in complement secretion by marrow, monocyte, and tissue macrophages detected with an improved hemolytic plaque assay.
    J Immunol. 1983 Jan;130(1):102-7 PMID: 6336622
  2. In vitro synthesis of M and Z forms of human alpha 1-antitrypsin.
    FEBS Lett. 1982 Nov 1;148(1):83-6 PMID: 6983458
  3. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed.
    Mol Cell Biol. 1983 May;3(5):787-95 PMID: 6865942
  4. alpha 1-antitrypsin deficiency detection by direct analysis of the mutation in the gene.
    Nature. 1983 Jul 21-27;304(5923):230-4 PMID: 6306478
  5. The effect of tamoxifen in intermediate alpha 1-antitrypsin deficiency associated with the phenotype PiSZ.
    Ann Clin Res. 1983 Apr;15(2):95-8 PMID: 6603815
  6. Human plasma proteinase inhibitors.
    Annu Rev Biochem. 1983;52:655-709 PMID: 6193754
  7. Translation and processing of normal (PiMM) and abnormal (PiZZ) human alpha 1-antitrypsin.
    FEBS Lett. 1983 Mar 21;153(2):270-4 PMID: 6604664
  8. Leucocyte-associated plasma proteins. Association of prealbumin, albumin, orosomucoid, alpha 1-antitrypsin, transferrin and haptoglobin with human lymphocytes, monocytes, granulocytes and a promyelocytic leukaemic cell line (HL-60).
    Scand J Clin Lab Invest. 1983 Feb;43(1):49-59 PMID: 6604935
  9. The elastase-antielastase hypothesis of the pathogenesis of emphysema.
    Clin Chest Med. 1983 Sep;4(3):405-12 PMID: 6196148
  10. Quick-blot: selective mRNA or DNA immobilization from whole cells.
    DNA. 1983;2(3):243-54 PMID: 6641475
  11. The isolation of a clone for human alpha 1-antitrypsin and the detection of alpha 1-antitrypsin in mRNA from liver and leukocytes.
    Biochem Biophys Res Commun. 1983 Oct 31;116(2):375-82 PMID: 6606425
  12. Expression of human alpha 1-antitrypsin in Escherichia coli.
    FEBS Lett. 1984 Jan 23;166(1):67-70 PMID: 6319192
  13. Dynamic response of alpha1-antitrypsin variants to diethylstilbestrol.
    Am J Hum Genet. 1973 Nov;25(6):610-7 PMID: 4543998
  14. Ribonucleic acid isolated by cesium chloride centrifugation.
    Biochemistry. 1974 Jun 4;13(12):2633-7 PMID: 4831907
  15. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels.
    Eur J Biochem. 1974 Jul 1;46(1):83-8 PMID: 4850204
  16. Alpha1-antitrypsin and its deficiency.
    Am Rev Respir Dis. 1974 Aug;110(2):176-94 PMID: 4212922
  17. Alpha-1-antitrypsin content in the serum, alveolar macrophages, and alveolar lavage fluid of smoking and nonsmoking normal subjects.
    J Clin Invest. 1975 Feb;55(2):427-30 PMID: 1079211
  18. Liver in alpha1-antitrypsin deficiency: morphologic observations and in vitro synthesis of alpha1-antitrypsin.
    Pediatr Res. 1976 Jan;10(1):35-40 PMID: 1082120
  19. Diethyl pyrocarbonate in nucleic acid research.
    Prog Nucleic Acid Res Mol Biol. 1976;16:189-262 PMID: 2947
  20. Molecular abnormality of human alpha1-antitrypsin variant (Pi-ZZ) associated with plasma activity deficiency.
    Proc Natl Acad Sci U S A. 1976 Apr;73(4):1324-8 PMID: 1083527
  21. Rapid identification of monocytes in a mixed mononuclear cell preparation.
    J Immunol Methods. 1977;14(3-4):267-9 PMID: 65435
  22. In vitro synthesis of alpha-1-antitrypsin in long term monolayer human liver cell cultures.
    Biomedicine. 1977 Apr;27(3):116-9 PMID: 302126
  23. Small airways in idiopathic pulmonary fibrosis. Comparison of morphologic and physiologic observations.
    J Clin Invest. 1977 Sep;60(3):595-610 PMID: 893665
  24. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination.
    Biochemistry. 1977 Oct 18;16(21):4743-51 PMID: 911786
  25. The separation, long-term cultivation, and maturation of the human monocyte.
    J Exp Med. 1977 Dec 1;146(6):1613-26 PMID: 925613
  26. Synthesis of antithrombin III and alpha-1-antitrypsin by the perfused rat liver.
    Biochim Biophys Acta. 1978 Apr 3;539(4):496-504 PMID: 305791
  27. Organ cultures of human fetal hepatocytes in the study of extra-and intracellular alpha1-antitrypsin.
    Biochim Biophys Acta. 1978 Sep 6;542(3):496-505 PMID: 308378
  28. A simple, sensitive assay for determining DNA in mononuclear phagocytes and other leukocytes.
    J Immunol Methods. 1978;23(1-2):169-73 PMID: 701811
  29. alpha1-antitrypsin deficiency (first of two parts).
    N Engl J Med. 1978 Nov 9;299(19):1045-8 PMID: 360063
  30. Separator isoelectric focusing for identification of alpha-1-antitrypsin (Pi M) subtypes.
    Scand J Clin Lab Invest. 1978 Sep;38(5):457-62 PMID: 30163
  31. Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state.
    J Exp Med. 1979 Jun 1;149(6):1504-18 PMID: 448291
  32. In vitro activation of a human macrophage-like cell line.
    Nature. 1979 May 24;279(5711):328-31 PMID: 450085
  33. Characteristics of human mononuclear phagocytes.
    Blood. 1979 Aug;54(2):485-500 PMID: 454850
  34. Morphological identification of alpha-1-antitrypsin in pulmonary macrophages.
    Hum Pathol. 1979 May;10(3):345-7 PMID: 313895
  35. Carbohydrate composition of normal and variant human alpha 1-protease inhibitors.
    Arch Biochem Biophys. 1979 Jul;195(2):591-5 PMID: 475401
  36. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.
    Am J Pathol. 1979 Oct;97(1):149-206 PMID: 495693
  37. Inhibition of intractable nucleases with ribonucleoside--vanadyl complexes: isolation of messenger ribonucleic acid from resting lymphocytes.
    Biochemistry. 1979 Nov 13;18(23):5143-9 PMID: 497174
  38. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  39. Secretion of alpha 1-antitrypsin by an established human hepatoma cell line and by human/mouse hybrids.
    Somatic Cell Genet. 1980 Jan;6(1):1-14 PMID: 6245472
  40. Report of Nomenclature Meeting for alpha 1-antitrypsin, INSERM, Rouen/Bois-Guillaume-1978.
    Hum Genet. 1980;53(3):429-33 PMID: 6102963
  41. Control of collagen production by human diploid lung fibroblasts.
    J Biol Chem. 1980 Jun 10;255(11):5250-60 PMID: 7372635
  42. The analysis of nucleic acids in gels using glyoxal and acridine orange.
    Methods Enzymol. 1980;65(1):380-91 PMID: 6154866
  43. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose.
    Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201-5 PMID: 6159641
  44. Pi M4: an additional Pi M subtype.
    Hum Genet. 1980;55(1):119-21 PMID: 6969686
  45. Characterization of the oligosaccharides of liver Z variant alpha 1-antitrypsin.
    Can J Biochem. 1980 Aug;58(8):644-8 PMID: 6970063
  46. Regulation of human peripheral blood monocyte DR antigen expression in vitro by lymphokines and recombinant interferons.
    J Clin Invest. 1984 Feb;73(2):556-65 PMID: 6230374
  47. High-level production of biologically active human alpha 1-antitrypsin in Escherichia coli.
    Proc Natl Acad Sci U S A. 1984 Feb;81(3):669-73 PMID: 6322161
  48. Xenopus oocytes can synthesise but do not secrete the Z variant of human alpha 1-antitrypsin.
    FEBS Lett. 1984 Mar 12;168(1):84-8 PMID: 6200362
  49. Leucocyte-associated plasma proteins in leucocytes during disease states, and in leukaemic cells.
    Scand J Clin Lab Invest. 1984 May;44(3):257-65 PMID: 6610201
  50. Hybridization of nucleic acids immobilized on solid supports.
    Anal Biochem. 1984 May 1;138(2):267-84 PMID: 6204550
  51. Rat lung tissue is a site of alpha 1-proteinase inhibitor synthesis: evidence by cell-free translation.
    Biochem Biophys Res Commun. 1984 Jul 18;122(1):394-400 PMID: 6146318
  52. Alveolar macrophage replication. One mechanism for the expansion of the mononuclear phagocyte population in the chronically inflamed lung.
    J Clin Invest. 1984 Aug;74(2):460-9 PMID: 6746904
  53. Production of growth factor activity for fibroblasts by human monocyte-derived macrophages.
    J Leukoc Biol. 1984 Aug;36(2):143-59 PMID: 6589336
  54. Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function.
    J Mol Biol. 1984 Aug 15;177(3):531-57 PMID: 6332197
  55. Expression of transferrin receptors and intracellular ferritin during terminal differentiation of human monocytes.
    Blut. 1984 Sep;49(3):195-202 PMID: 6089939
  56. Accurate quantification of cells recovered by bronchoalveolar lavage.
    Am Rev Respir Dis. 1984 Oct;130(4):650-8 PMID: 6385789
  57. Murine monocytes express transferrin receptors: evidence for similarity to inflammatory macrophages.
    Cell Immunol. 1984 Oct 15;88(2):343-9 PMID: 6091922
  58. Expression of the MHC class III genes.
    Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):355-66 PMID: 6149578
  59. Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant.
    Biochemistry. 1984 Oct 9;23(21):4828-37 PMID: 6093867
  60. Normal human alveolar macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin-1.
    J Clin Invest. 1984 Dec;74(6):2208-18 PMID: 6334697
  61. An evolutionary switch in tissue-specific gene expression. Abundant expression of alpha 1-antitrypsin in the kidney of a wild mouse species.
    J Biol Chem. 1985 Jan 25;260(2):1160-5 PMID: 2981835
  62. Tissue-specific pretranslational regulation of complement production in human mononuclear phagocytes.
    J Immunol. 1985 Apr;134(4):2610-6 PMID: 3844437
  63. Expression of the alpha 1-proteinase inhibitor gene in human monocytes and macrophages.
    Proc Natl Acad Sci U S A. 1985 Feb;82(3):795-9 PMID: 3871944
  64. The cellular defect in alpha 1-proteinase inhibitor (alpha 1-PI) deficiency is expressed in human monocytes and in Xenopus oocytes injected with human liver mRNA.
    Proc Natl Acad Sci U S A. 1985 Oct;82(20):6918-21 PMID: 3876562
  65. The nucleic-acid content of the cell.
    Lancet. 1951 Jun 16;1(6668):1287-90 PMID: 14842059
  66. INCREASE OF TRYPSIN INHIBITOR IN SERUM DURING PREGNANCY.
    Nature. 1963 Jul 20;199:290-1 PMID: 14076697
  67. PULMONARY EMPHYSEMA AND ALPHA1-ANTITRYPSIN DEFICIENCY.
    Acta Med Scand. 1964 Feb;175:197-205 PMID: 14124635
  68. The determination of nucleic acids.
    Methods Biochem Anal. 1966;14:113-76 PMID: 5328501
  69. Alpha-1-antitrypsin and alpha-2-macroglobulin concentration in serum during pregnancy.
    Acta Obstet Gynecol Scand. 1967;46(2):126-37 PMID: 6060002
  70. Effect of administration of a combined estrogen-progestin contraceptive on the level of individual plasma proteins.
    Scand J Clin Lab Invest. 1968;21(4):337-43 PMID: 4178691
  71. Genetically determined differences in the response of alpha-antitrypsin levels in human serum to typhoid vaccine.
    Humangenetik. 1968;6(3):207-14 PMID: 5709080
  72. Chromosome studies of virus-infected semi-continuous human embryonic liver cells.
    Br J Exp Pathol. 1970 Feb;51(1):92-6 PMID: 4985032
  73. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  74. Screening for heterozygous 1 -antitrypsin deficiency. 3. A provocative test with diethylstilbestrol and effect of oral contraceptives.
    JAMA. 1971 Aug 30;217(9):1198-206 PMID: 5109458
  75. Hydroxyapatite chromatography and formamide denaturation of adenovirus DNA.
    J Virol. 1973 Aug;12(2):218-25 PMID: 4355929
  76. Interrelationships between the human alveolar macrophage and alpha-1-antitrypsin.
    J Clin Invest. 1973 Nov;52(11):2793-9 PMID: 4201266
  77. Secretion of alpha 1-proteinase inhibitor by cultured rat alveolar macrophages.
    Am Rev Respir Dis. 1981 Apr;123(4 Pt 1):447-9 PMID: 6971590
  78. The Pi polymorphism: genetic, biochemical, and clinical aspects of human alpha 1-antitrypsin.
    Adv Hum Genet. 1981;11:1-62, 371-2 PMID: 6168185
  79. Alpha-1-antitrypsin in human macrophages.
    J Clin Pathol. 1981 Sep;34(9):982-90 PMID: 6792245
  80. Rat alpha 1-antitrypsin, preliminary characterisation of the in vitro mRNA translation product.
    FEBS Lett. 1981 Aug 3;130(2):297-300 PMID: 6974652
  81. Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema.
    J Clin Invest. 1981 Oct;68(4):889-98 PMID: 6169740
  82. [DNA content and cell number in heart and liver of children. Comparable biochemical, cytophotometric and histological investigations (author's transl)].
    Pathol Res Pract. 1981 Jul;172(1-2):25-41 PMID: 7312710
  83. Functional alpha 1 protease inhibitor produced by a human hepatoma cell line.
    J Lab Clin Med. 1982 Jan;99(1):108-17 PMID: 6274980
  84. Identification of the translation products of alpha -1-antitrypsin mRNA from baboon liver polysomes.
    FEBS Lett. 1982 Jan 25;137(2):231-5 PMID: 6174370
  85. A simple one-step purification of human alpha 1-proteinase inhibitor by immunoadsorbent column chromatography.
    J Biochem Biophys Methods. 1981 Dec;5(5):243-9 PMID: 7037919
  86. Assignment of human alpha 1-antitrypsin to chromosome 14 by somatic cell hybrid analysis.
    Proc Natl Acad Sci U S A. 1982 Feb;79(3):870-3 PMID: 6801664
  87. Sequence homology and structural comparison between the chromosomal human alpha 1-antitrypsin and chicken ovalbumin genes.
    Nature. 1982 Jun 24;297(5868):655-9 PMID: 6979715
  88. Structure and variation of human alpha 1-antitrypsin.
    Nature. 1982 Jul 22;298(5872):329-34 PMID: 7045697
  89. Cell number and cell characteristics of the normal human lung.
    Am Rev Respir Dis. 1982 Aug;126(2):332-7 PMID: 7103258
  90. Synthesis of alpha 1-antitrypsin in rat-liver hepatocytes and in a cell-free system.
    Eur J Biochem. 1982 Aug;126(1):189-95 PMID: 6982162
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI112524
Published
1986-06-00
Pages
1952-61
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC370556
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI112524 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2