Journal of Environmental Health Sciences (한국환경보건학회지)

Korean Society of Environmental Health (한국환경보건학회)
권호 표지
DOI QR코드

DOI QR Code

Exposure to Environmental Endotoxin and Health Effects

환경 중의 엔도톡신 노출 및 건강에 미치는 영향

  • Park, Ju-Hyeong (Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health)
  • 박주형 (미국 직업안전보건연구원)
  • Received : 2014.07.03
  • Accepted : 2014.08.18
  • Published : 2014.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Microbes such as bacteria, fungi, archaea, protists, and viruses are ubiquitous and people are exposed to them continuously. Endotoxin is a component of the outer membrane of Gram-negative bacteria and a potent proinflammaotry substance. When a person is exposed to environmental endotoxin, an innate immune response is initiated upon the initial recognition and this response produces various inflammatory mediators and recruits inflammatory cells to the exposed tissues. A purified chemical form of endotoxin is called lipopolysaccharide (LPS), and the lipid A portion of the molecule is a biologically active moiety. Exposure to endotoxin may result in various complex health effects depending on time, route, and dose of exposure, as well as host susceptibility. Gene-environment interactions play important roles in health effects of endotoxin exposure, e.g. development or aggravation of asthma. To accurately assess exposure to endotoxin in environmental or epidemiologic studies, methods of sampling, extraction, and analysis must be carefully selected since the selected methods may substantially affect analytical results and there is no internationally-agreed standard method to date. The lack of a standardized method hampers the establishment of exposure-response relationships. While an internationally-agreed health-based exposure limit does not exist, the Dutch Expert Committee on Occupational Safety recently recommended $90EU/m^3$ as a health-based occupational exposure limit. The current article reviews various scientific issues on how we measure environmental endotoxin and the health effects of endotoxin exposure.

Keywords

References

  1. Simpson JL, Brooks C, Douwes J. Innate immunity in asthma. Pediatr Respir Rev. 2008; 9: 263-270. https://doi.org/10.1016/j.prrv.2008.05.007
  2. Dawson ME. Depyrogenation. Hillerod: Incoporated Press; 1993.
  3. Heumann D, Roger T. Initial responses to endotoxins and Gram-negative bacteria. Clin Chim Acta. 2002; 323(1-2): 59-72. https://doi.org/10.1016/S0009-8981(02)00180-8
  4. Rietschel ET, Brade H. Bacterial endotoxins. Sci Am. 1992; 267(2): 54-61.
  5. Beutler B, Rietschel ET. Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol. 2003; 3(2): 169-176. https://doi.org/10.1038/nri1004
  6. Shear MJ, Turner FC. Chemical treatment of tumors. V. Isolation of the hemorrhage-producing fraction from Serratia marcescens (Cacillus prodigiosus) culture filtrates. J Natl Cancer Inst. 1943; 4(1): 81-97.
  7. Duquenne P, Marchand G, Duchaine C. Measurement of endotoxins in bioaerosols at workplace: a critical review of literature and a standardization issue. Ann Occup Hyg. 2013; 57(2): 137-172. https://doi.org/10.1093/annhyg/mes051
  8. Alexander C, Rietschel ET. Bacterial lipopolysac-charides and innate immunity. J Endotoxin Res. 2001; 7(3): 167-202.
  9. Gioannini TL, Weiss JP. Regulation of interactions of Gram-negative bacterial endotoxins with mammalian cells. Immunol Res. 2007; 39(1-3): 249-260. https://doi.org/10.1007/s12026-007-0069-0
  10. Bentala H, Verweij WR, Huizinga-Van der Vlag A, van Loenen-Weemaes AM, Meijer DK, Poelstra K. Removal of phosphate from lipid A as a strategy to detoxify lipopolysaccharide. Shock. 2002; 18(6): 561-566. https://doi.org/10.1097/00024382-200212000-00013
  11. Netea MG, van DM, Kullberg BJ, Cavaillon JM, Van der Meer JW. Does the shape of lipid A determine the interaction of LPS with Toll-like receptors?. Trends Immunol. 2002; 23(3): 135-139. https://doi.org/10.1016/S1471-4906(01)02169-X
  12. Saraf A, Larsson L, Burge H, Milton D. Quantification of ergosterol and 3-hydroxy fatty acids in settled house dust by gas chromatography-mass spectrometry: Comparison with fungal culture and determination of endotoxin by a Limulus amebocyte lysate assay. Appl Environ Microbiol. 1997; 63(7): 2554-2559.
  13. Gioannini TL, Teghanemt A, Zhang D, Levis EN, Weiss JP. Monomeric endotoxin:protein complexes are essential for TLR4-dependent cell activation. J Endotoxin Res. 2005; 11(2): 117-123. https://doi.org/10.1177/09680519050110020801
  14. Rylander R. Endotoxin in the environment--exposure and effects. J Endotoxin Res. 2002; 8(4): 241-252.
  15. Bang FB. Rules and regulations regarding serendipity. Prog Clin Biol Res. 1982; 93: 1-5.
  16. Cohen E, Bang F, Levin J. Biomedical applications of the horseshoe crab (Limulidae). New York: The University of Michigan Press; 1979.
  17. US Department of Health and Human Services. Guidance for industry, Pyrogen and endotoxins testing: questions and answers. Maryland: US Department of Health and Human Services Press; 2012.
  18. The Unitied States Pharmacopeial Convention. <85> Bacterial endotoxins test. USA: The United States Pharmacopeial Convention Press; 2011.
  19. Novitsky TJ. Endotoxins Facts and Fiction: Endotoxin as a component of the bacterial cell. USA: Associates of Cape Cod Press; 1998.
  20. Dawson M. Interference with the LAL test and how to address it. USA: Associates of Cape Cod Press; 2005.
  21. Milton DK, Johnson DK, Park JH. Environmental endotoxin measurement: Interference and sources of variation in the Limulus assay of house dust. Am Ind Hyg Assoc J. 1997; 58(12): 861-867. https://doi.org/10.1080/15428119791012199
  22. Milton DK, Gere RJ, Feldman HA, Greaves IA. Endotoxin Measurement:Aaerosol sampling and application of a new Limulus method. Am Ind Hyg Assoc J. 1990; 51(6): 331-337. https://doi.org/10.1080/15298669091369754
  23. Milton DK, Feldman HA, Neuberg DS, Bruckner RJ, Greaves IA. Environmental endotoxin measurement: The kinetic Limulus assay with resistant-parallel-line estimation. Environ Res. 1992; 57(2): 212-230. https://doi.org/10.1016/S0013-9351(05)80081-7
  24. Chen L. Pyrogen-a new endotoxin detection method using recombinant Factor C. The 5th International Symposium on Future of Rural Peoples: rural economy, healthy people, environment, rural comunities. 2003.
  25. Alwis KU, Milton DK. Recombinant factor C assay for measuring endotoxin in house dust: comparison with LAL, and (1 $\rightarrow$ 3)-beta-D-glucans. Am J Ind Med. 2006; 49(4): 296-300. https://doi.org/10.1002/ajim.20264
  26. Novitsky TJ. LAL: Discovery and commercial development. USA: Associates of Cape Cod, Incorporated Press; 1996.
  27. Binding N, Jaschinski S, Werlich S, Bletz S, Witting U. Quantification of bacterial lipopolysaccharides (endotoxin) by GC-MS determination of 3-hydroxy fatty acids. J Environ Monitor. 2004; 6(1): 65-70. https://doi.org/10.1039/b309237b
  28. Mielniczuk Z, Mielniczuk E, Larsson L. Gas chromatography-mass spectrometry methods for analysis of 2- and 3-hydroxylated fatty acids: Application for endotoxin measurement. J Microbiol Methods. 1993; 17: 91-102. https://doi.org/10.1016/0167-7012(93)90002-Y
  29. Saraf A, Park JH, Milton DK, Larsson L. Use of quadrupole GC-MS and ion-trap GC-MSMS for determining 3-hydroxy fatty acids in settled house dust: Relation to endotoxin activity. J Environ Monitor. 1999; 2: 163-168.
  30. Chun DT, Chew V, Bartlett K, Gordon T, Jacobs R, Larsson BM, et al. Second inter-laboratory study comparing endotoxin assay results from cotton dust. Ann Agric Environ Med. 2002; 9(1): 49-53.
  31. Chun DT, Bartlett K, Gordon T, Jacobs RR, Larsson BM, Larsson L, et al. History and results of the two inter-laboratory round robin endotoxin assay studies on cotton dust. Am J Ind Med. 2006; 49(4): 301-306. https://doi.org/10.1002/ajim.20266
  32. Reynolds SJ, Thorne PS, Donham KJ, Croteau EA, Kelly KM, Lewis D, et al. Comparison of endotoxin assays using agricultural dusts. Am Ind Hyg Assoc J. 2002; 63(4): 430-438. https://doi.org/10.1080/15428110208984731
  33. Reynolds SJ, Milton DK, Heederik D, Thorne PS, Donham KJ, Croteau EA, et al. Interlaboratory evaluation of endotoxin analyses in agricultural dusts--comparison of LAL assay and mass spectrometry. J Environ Monitor. 2005; 7(12): 1371-1377. https://doi.org/10.1039/b509256f
  34. Chun DT, Chew V, Bartlett K, Gordon T, Jacobs RR, Larsson B-M, et al. Preliminary report on the results of the second pase of a round-robin endotoxin assay study using cotton dust. Appl Occup Environ Hyg. 2000; 15(1): 152-157. https://doi.org/10.1080/104732200301971
  35. Gordon T, Galdanes K, Brosseau L. Comparison of sampling media for endotoxin-containing aerosols. Appl Occup Environ Hyg. 1992; 7(7): 472-477. https://doi.org/10.1080/1047322X.1992.10390192
  36. Hailman E, Lichenstein HS, Wurfel MM, Miller DS, Johnson DA, Kelley M, et al. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med. 1994; 179(1): 269-277. https://doi.org/10.1084/jem.179.1.269
  37. Tobias PS, Soldau K, Kline L, Lee JD, Kato K, Martin TP, et al. Cross-linking of lipopolysaccharide (LPS) to CD14 on THP-1 cells mediated by LPS-binding protein. J Immunol. 1993; 150(7): 3011-3021.
  38. Wurfel MM, Kunitake ST, Lichenstein H, Kane JP, Wright SD. Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS. J Exp Med. 1994; 180(3): 1025-1035. https://doi.org/10.1084/jem.180.3.1025
  39. Yu B, Wright SD. Catalytic properties of lipopolysaccharide (LPS) binding protein. Transfer of LPS to soluble CD14. J Biol Chem. 1996; 271(8): 4100-4105. https://doi.org/10.1074/jbc.271.8.4100
  40. Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008; 42(2): 145-151. https://doi.org/10.1016/j.cyto.2008.01.006
  41. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990; 249(4975): 1431-1433. https://doi.org/10.1126/science.1698311
  42. Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature. 2009; 458(7242): 1191-1195. https://doi.org/10.1038/nature07830
  43. Park BS, Lee JO. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med. 2013; 45: e66, doi:10.1038/emm.2013.97.
  44. Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, et al. Structure and function of lipopolysaccharide binding protein. Science. 1990; 249(4975): 1429-1431. https://doi.org/10.1126/science.2402637
  45. Reed CE, Milton DK. Endotoxin-stimulated innate immunity: A contributing factor for asthma. J Allergy Clin Immunol. 2001; 108(2): 157-166. https://doi.org/10.1067/mai.2001.116862
  46. Dutkiewicz J, Krysinska-Traczyk E, Prazmo Z, Skorska C, Sitkowska J. Exposure to airborne microorganisms in Polish sawmills. Ann Agric Environ Med. 2001; 8(1): 71-80.
  47. Dutkiewicz J, Krysinska-Traczyk E, Skorska C, Cholewa G, Sitkowska J. Exposure to airborne microorganisms and endotoxin in a potato processing plant. Ann Agric Environ Med. 2002; 9(2): 225-235.
  48. Gora A, Mackiewicz B, Krawczyk P, Golec M, Skorska C, Sitkowska J, et al. Occupational exposure to organic dust, microorganisms, endotoxin and peptidoglycan among plants processing workers in Poland. Ann Agric Environ Med. 2009; 16(1): 143-150.
  49. Laitinen S, Kangas J, Husman K, Susitaival P. Evaluation of exposure to airborne bacterial endotoxins and peptidoglycans in selected work environments. Ann Agric Environ Med. 2001; 8(2): 213-9.
  50. Thorn J, Rylander R. Inflammatory response after inhalation of bacterial endotoxin assessed by the induced sputum technique. Thorax. 1998; 53(12): 1047-1052. https://doi.org/10.1136/thx.53.12.1047
  51. Michel O, Nagy AM, Schroeven M, Duchateau J, Neve J, Fondu P, et al. Dose-response relationship to inhaled endotoxin in normal subjects. Am J Respir Crit Care Med. 1997; 156(4 Pt 1): 1157-1164. https://doi.org/10.1164/ajrccm.156.4.97-02002
  52. Rylander R, Haglind P. Airborne endotoxins and humidifier disease. Clin Allergy. 1984; 14: 109-112. https://doi.org/10.1111/j.1365-2222.1984.tb02197.x
  53. Castellan RM, Olenchock SA, Kinsley KB, Hankinson JL. Inhaled endotoxin and decreased spirometric values, an exposure-response relation for cotton dust. New Engl J Med. 1987; 317: 605-610. https://doi.org/10.1056/NEJM198709033171005
  54. Donham K, Haglind P, Peterson Y, Rylander R, Belin L. Environmental and health studies of farm workers in Swedish swine confinement buildings. Br J Ind Med. 1989; 46(1): 31-37.
  55. Dutch Expert Committee on Occupational Safety. Endotoxins: Health-based recommended occupational exposure limit. Netherland: The Health Council of the Netherlands Press; 2010.
  56. Milton DK, Wypij D, Kriebel D, Walters M, Hammond SK, Evans J. Endotoxin exposure-response in a fiberglass manufacturing plant. Am J Ind Med. 1996; 29: 3-13. https://doi.org/10.1002/(SICI)1097-0274(199601)29:1<3::AID-AJIM2>3.0.CO;2-V
  57. Douwes J, Gibson P, Pekkanen J, Pearce N. Noneosinophilic asthma: importance and possible mechanisms. Thorax. 2002; 57(7): 643-648. https://doi.org/10.1136/thorax.57.7.643
  58. Greisman SE, Hornick RB, Wagner HN, Woodward WE, Woodward TE. The role of endotoxin during typhoid fever and tularemia in man. IV. The integrity of the endotoxin tolerance mechanisms during infection. J Clin Invest. 1969; 48(4): 613-629. https://doi.org/10.1172/JCI106020
  59. Institute of Medicine CotAoAaIA. Clearing the air: Asthma and indoor air exposures. Washington D.C: National Academies Press; 2000.
  60. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the diagnosis and management of asthma. Bethesda: National Heart, Lung, and Blood IUnstitute Press: 2007.
  61. Park JH, Cox-Ganser JM. Mold exposure and respiratory health in damp indoor environments. Front Biosci (Elite Edition). 2011; 3: 757-771. https://doi.org/10.2741/e284
  62. Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012; 18(5): 673-683. https://doi.org/10.1038/nm.2731
  63. Pearce N, Pekkanen J, Beasley R. How much asthma is really attributable to atopy?. Thorax. 1999; 54(3): 268-272. https://doi.org/10.1136/thx.54.3.268
  64. Weinmayr G, Weiland SK, Bjorksten B, Brunekreef B, Buchele G, Cookson WO, et al. Atopic sensitization and the international variation of asthma symptom prevalence in children. Am J Respir Crit Care Med. 2007; 176(6): 565-574. https://doi.org/10.1164/rccm.200607-994OC
  65. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989; 299(6710): 1259-1260. https://doi.org/10.1136/bmj.299.6710.1259
  66. Eduard W, Omenaas E, Bakke PS, Douwes J, Heederik D. Atopic and non-atopic asthma in a farming and a general population. Am J Ind Med. 2004; 46(4): 396-399. https://doi.org/10.1002/ajim.20088
  67. Braun-Fahrlander C, Riedler J, Herz U, Eder W, Waser M, Grize L, et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. New Engl J Med. 2002; 347(12): 869-877. https://doi.org/10.1056/NEJMoa020057
  68. Gehring U, Bolte G, Borte M, Bischof W, Fahlbusch B, Wichmann HE, et al. Exposure to endotoxin decreases the risk of atopic eczema in infancy: a cohort study. J Allergy Clin Immunol. 2001; 108(5): 847-854. https://doi.org/10.1067/mai.2001.119026
  69. Gereda JE, Leung DY, Thatayatikom A, Streib JE, Price MR, Klinnert MD, et al. Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet. 2000; 355(9216): 1680-1683. https://doi.org/10.1016/S0140-6736(00)02239-X
  70. Park JH, Gold DR, Spiegelman DL, Burge HA, Milton DK. House dust endotoxin and wheeze in the first year of life. Am J Respir Crit Care Med. 2001; 163(2): 322-328. https://doi.org/10.1164/ajrccm.163.2.2002088
  71. Martinez FD. CD14, endotoxin, and asthma risk: actions and interactions. Proc Am Thorac Soc. 2007; 4(3): 221-225. https://doi.org/10.1513/pats.200702-035AW
  72. Koppelman GH, Postma DS. The genetics of CD14 in allergic disease. Curr Opin Allergy Clin Immunol. 2003; 3(5): 347-352. https://doi.org/10.1097/00130832-200310000-00005
  73. Martinez FD, Holt PG. Role of microbial burden in aetiology of allergy and asthma. Lancet. 1999; 354(Suppl 2): SII12-SII15. https://doi.org/10.1016/S0140-6736(99)90437-3
  74. Kiley JP, Caler EV. The lung microbiome. A new frontier in pulmonary medicine. Ann Am Thorac Soc. 2014; 11 (Suppl 1): S66-S70. https://doi.org/10.1513/AnnalsATS.201308-285MG
  75. Anderson WB, George DD, Mayfield CI. Estimation of endotoxin inhalation from shower and humidifier exposure reveals potential risk to human health. J Water Health. 2007; 5(4): 553-572 https://doi.org/10.2166/wh.2007.043
  76. Park JH, Spiegelman DL, Burge HA, Gold DR, Chew GL, Milton DK. Longitudinal study of dust and airborne endotoxin in the home. Environ Health Perspect. 2000; 108(11): 1023-1028. https://doi.org/10.1289/ehp.001081023
  77. Abraham JH, Finn PW, Milton DK, Ryan LM, Perkins DL, Gold DR. Infant home endotoxin is associated with reduced allergen-stimulated lymphocyte proliferation and IL-13 production in childhood. J Allergy Clin Immunol. 2005; 116(2): 431-437. https://doi.org/10.1016/j.jaci.2005.05.015
  78. Zambelli-Weiner A, Ehrlich E, Stockton ML, Grant AV, Zhang S, Levett PN, et al. Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study. J Allergy Clin Immunol. 2005; 115(6): 1203-1209. https://doi.org/10.1016/j.jaci.2005.03.001
  79. Ohnishi H, Yokoyama A, Hamada H, Manabe S, Ito R, Watanabe A, et al. Humidifier lung: possible contribution of endotoxin-induced lung injury. Intern Med. 2002; 41(12): 1179-1182. https://doi.org/10.2169/internalmedicine.41.1179
  80. Park JH, Cox-Ganser JM, Rao CY, Kreiss K. Fungal and endotoxin measurements in dust associated with respiratory symptoms in a water-damaged office building. Indoor Air. 2006; 16(3): 192-203. https://doi.org/10.1111/j.1600-0668.2005.00415.x
  81. Hasday JD, Bascom R, Costa JJ, Fitzgerald T, Dubin W. Bacterial endotoxin is an active component of cigarette smoke. Chest. 1999; 115(3): 829-835. https://doi.org/10.1378/chest.115.3.829
  82. Larsson L, Szponar B, Pehrson C. Tobacco smoking increases dramatically air concentrations of endotoxin. Indoor Air. 2004; 14(6): 421-424. https://doi.org/10.1111/j.1600-0668.2004.00290.x
  83. Sebastian A, Pehrson C, Larsson L. Elevated concentrations of endotoxin in indoor air due to cigarette smoking. J Environ Monitor. 2006; 8(5): 519-522. https://doi.org/10.1039/b600706f
  84. Pavilonis BT, Anthony TR, O'Shaughnessy PT, Humann MJ, Merchant JA, Moore G, et al. Indoor and outdoor particulate matter and endotoxin concentrations in an intensely agricultural county. J Expo Sci Environ Epidemiol. 2013; 23(3): 299-305. https://doi.org/10.1038/jes.2012.123
  85. American Conference of Governmental Industrial Hygienists. Bioaerosols: Ohio: ACGIH Press; 1999.
  86. Carroll IM, Threadgill DW, Threadgill DS. The gastrointestinal microbiome: a malleable, third genome of mammals. Mamm Genome. 2009; 20(7): 395-403. https://doi.org/10.1007/s00335-009-9204-7
  87. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nature Rev Genet. 2012; 13(4): 260-270.
  88. Pflughoeft KJ, Versalovic J. Human microbiome in health and disease. Annu Rev Pathol. 2012; 7: 99-122. https://doi.org/10.1146/annurev-pathol-011811-132421