• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Jan 1986; 77(1): 54–60.
PMCID: PMC423308

Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro.

Abstract

Recent studies have shown that alveolar macrophages (AM) are able to release leukotrienes (LTs). Since cigarette smoking inhibits the cyclooxygenase pathway of arachidonic acid metabolism in the AM, we evaluated the LT production by AM from smokers and nonsmokers. AM were obtained from 35 volunteers, 16 nonsmokers, and 19 smokers. The cells were incubated under various conditions including stimulation with 30 microM arachidonic acid, 2 microM ionophore A23187, or both. Each experiment was performed in parallel using cells from a smoker and a nonsmoker. Lipoxygenase products were analyzed by reverse-phase high performance liquid chromatography. After stimulation, nonsmokers' AM produced LTB4 and 5-hydroxy-eicosatetraenoic acid (5-HETE). In incubations of AM with arachidonic acid and ionophore, the amounts of products formed were: LTB4, 317 +/- 56 pmol/10(6) cells and 5-HETE, 1,079 +/- 254, mean +/- SEM. No metabolites were generated under control conditions (no stimulation). In all incubations performed, the peptido-LTs (LTC4, LTD4, and LTE4) were undetectable. In comparison with AM from nonsmokers, those from smokers showed a 80-90% reduction of 5-HETE and LTB4 synthesis (P less than 0.05 to P less than 0.001 according to stimulatory conditions). This defective lipoxygenase metabolite production in AM from smokers was observed over a wide range of stimuli concentrations and incubation times; AM from smokers also had lower levels of intracellular (esterified) 5-HETE than nonsmokers' AM. We also studied blood polymorphonuclear leukocytes (PMNL) and no difference in the synthesis of 5-lipoxygenase products in these cells was noticed between smokers and nonsmokers. These data show that cigarette smoking causes a profound inhibition of the 5-lipoxygenase pathway in AM but not in blood PMNL.

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 (1.2M), 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.
  • Harris JO, Swenson EW, Johnson JE., 3rd Human alveolar macrophages: comparison of phagocytic ability, glucose utilization, and ultrastructure in smokers and nonsmokers. J Clin Invest. 1970 Nov;49(11):2086–2096. [PMC free article] [PubMed]
  • Pratt SA, Smith MH, Ladman AJ, Finley TN. The ultrastructure of alveolar macrophages from human cigarette smokers and nonsmokers. Lab Invest. 1971 May;24(5):331–338. [PubMed]
  • Warr GA, Martin RR. Histochemical staining and in vitro spreading of human pulmonary alveolar macrophages: variability with cigarette smoking status. J Reticuloendothel Soc. 1978 Jan;23(1):53–62. [PubMed]
  • Hoidal JR, Niewoehner DE. Lung phagocyte recruitment and metabolic alterations induced by cigarette smoke in humans and in hamsters. Am Rev Respir Dis. 1982 Sep;126(3):548–552. [PubMed]
  • Green GM, Jakab GJ, Low RB, Davis GS. Defense mechanisms of the respiratory membrane. Am Rev Respir Dis. 1977 Mar;115(3):479–514. [PubMed]
  • Kazmierowski JA, Gallin JI, Reynolds HY. Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage-derived chemotactic factor with preferential activity for polymorphonuclear leukocytes. J Clin Invest. 1977 Feb;59(2):273–281. [PMC free article] [PubMed]
  • Reynolds HY. Lung inflammation: role of endogenous chemotactic factors in attracting polymorphonuclear granulocytes. Am Rev Respir Dis. 1983 Feb;127(2):S16–S25. [PubMed]
  • Fels AO, Pawlowski NA, Cramer EB, King TK, Cohn ZA, Scott WA. Human alveolar macrophages produce leukotriene B4. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7866–7870. [PMC free article] [PubMed]
  • Martin TR, Altman LC, Albert RK, Henderson WR. Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung. Am Rev Respir Dis. 1984 Jan;129(1):106–111. [PubMed]
  • Borgeat P, Sirois P. Leukotrienes: a major step in the understanding of immediate hypersensitivity reactions. J Med Chem. 1981 Feb;24(2):121–126. [PubMed]
  • Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith MJ. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. [PubMed]
  • Bray MA, Ford-Hutchinson AW, Smith MJ. Leukotriene B4: an inflammatory mediator in vivo. Prostaglandins. 1981 Aug;22(2):213–222. [PubMed]
  • Borgeat P, Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A. 1979 May;76(5):2148–2152. [PMC free article] [PubMed]
  • Borgeat P, Samuelsson B. Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. Formation of a novel dihydroxyeicosatetraenoic acid. J Biol Chem. 1979 Apr 25;254(8):2643–2646. [PubMed]
  • Borgeat P, Fruteau de Laclos B, Rabinovitch H, Picard S, Braquet P, Hébert J, Laviolette M. Eosinophil-rich human polymorphonuclear leukocyte preparations characteristically release leukotriene C4 on ionophore A23187 challenge. J Allergy Clin Immunol. 1984 Sep;74(3 Pt 2):310–315. [PubMed]
  • Pawlowski NA, Kaplan G, Hamill AL, Cohn ZA, Scott WA. Arachidonic acid metabolism by human monocytes. Studies with platelet-depleted cultures. J Exp Med. 1983 Aug 1;158(2):393–412. [PMC free article] [PubMed]
  • Goldyne ME, Burrish GF, Poubelle P, Borgeat P. Arachidonic acid metabolism among human mononuclear leukocytes. Lipoxygenase-related pathways. J Biol Chem. 1984 Jul 25;259(14):8815–8819. [PubMed]
  • Rouzer CA, Scott WA, Cohn ZA, Blackburn P, Manning JM. Mouse peritoneal macrophages release leukotriene C in response to a phagocytic stimulus. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4928–4932. [PMC free article] [PubMed]
  • Jubiz W, Rådmark O, Malmsten C, Hansson G, Lindgren JA, Palmblad J, Udén AM, Samuelsson B. A novel leukotriene produced by stimulation of leukocytes with formylmethionylleucylphenylalanine. J Biol Chem. 1982 Jun 10;257(11):6106–6110. [PubMed]
  • Laviolette M, Chang J, Newcombe DS. Human alveolar macrophages: a lesion in arachidonic acid metabolism in cigarette smokers. Am Rev Respir Dis. 1981 Oct;124(4):397–401. [PubMed]
  • Haynes WF, Jr, Krstulovic VJ, Bell AL., Jr Smoking habit and incidence of respiratory tract infections in a group of adolescent males. Am Rev Respir Dis. 1966 May;93(5):730–735. [PubMed]
  • Parnell JL, Anderson DO, Kinnis C. Cigarette smoking and respiratory infections in a class of student nurses. N Engl J Med. 1966 May 5;274(18):979–984. [PubMed]
  • Laviolette M. Lymphocyte fluctuation in bronchoalveolar lavage fluid in normal volunteers. Thorax. 1985 Sep;40(9):651–656. [PMC free article] [PubMed]
  • Damon M, Chavis C, Godard P, Michel FB, Crastes de Paulet A. Purification and mass spectrometry identification of leukotriene D4 synthesized by human alveolar macrophages. Biochem Biophys Res Commun. 1983 Mar 16;111(2):518–524. [PubMed]
  • MacDermot J, Kelsey CR, Waddell KA, Richmond R, Knight RK, Cole PJ, Dollery CT, Landon DN, Blair IA. Synthesis of leukotriene B4, and prostanoids by human alveolar macrophages: analysis by gas chromatography/mass spectrometry. Prostaglandins. 1984 Feb;27(2):163–179. [PubMed]
  • Fruteau de Laclos B, Braquet P, Borgeat P. Characteristics of leukotriene (LT) and hydroxy eicosatetraenoic acid (HETE) synthesis in human leukocytes in vitro: effect of arachidonic acid concentration. Prostaglandins Leukot Med. 1984 Jan;13(1):47–52. [PubMed]
  • Goetzl EJ. Selective feed-back inhibition of the 5-lipoxygenation of arachidonic acid in human T-lymphocytes. Biochem Biophys Res Commun. 1981 Jul 30;101(2):344–350. [PubMed]
  • Powell WS. Properties of leukotriene B4 20-hydroxylase from polymorphonuclear leukocytes. J Biol Chem. 1984 Mar 10;259(5):3082–3089. [PubMed]
  • Nadeau M, Fruteau de Laclos B, Picard S, Braquet P, Corey EJ, Borgeat P. Studies on leukotriene B4 omega-oxidation in human leukocytes. Can J Biochem Cell Biol. 1984 Dec;62(12):1321–1326. [PubMed]
  • Stenson WF, Parker CW. Metabolism of arachidonic acid in ionophore-stimulated neutrophils. Esterification of a hydroxylated metabolite into phospholipids. J Clin Invest. 1979 Nov;64(5):1457–1465. [PMC free article] [PubMed]
  • Pawlowski NA, Scott WA, Andreach M, Cohn ZA. Uptake and metabolism of monohydroxy-eicosatetraenoic acids by macrophages. J Exp Med. 1982 Jun 1;155(6):1653–1664. [PMC free article] [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...