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http://dx.doi.org/10.5668/JEHS.2014.40.4.265

Exposure to Environmental Endotoxin and Health Effects  

Park, Ju-Hyeong (Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health)
Publication Information
Journal of Environmental Health Sciences / v.40, no.4, 2014 , pp. 265-278 More about this Journal
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
Asthma; Endotoxin; Hygiene hypothesis; Innate immune system; LPS;
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1 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.   DOI
2 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.
3 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.
4 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.   DOI
5 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.   DOI
6 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.   DOI
7 Gordon T, Galdanes K, Brosseau L. Comparison of sampling media for endotoxin-containing aerosols. Appl Occup Environ Hyg. 1992; 7(7): 472-477.   DOI
8 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.   DOI   ScienceOn
9 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.   DOI
10 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.   DOI   ScienceOn
11 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.   DOI   ScienceOn
12 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.   DOI
13 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.   DOI
14 Larsson L, Szponar B, Pehrson C. Tobacco smoking increases dramatically air concentrations of endotoxin. Indoor Air. 2004; 14(6): 421-424.   DOI
15 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.   DOI
16 American Conference of Governmental Industrial Hygienists. Bioaerosols: Ohio: ACGIH Press; 1999.
17 Carroll IM, Threadgill DW, Threadgill DS. The gastrointestinal microbiome: a malleable, third genome of mammals. Mamm Genome. 2009; 20(7): 395-403.   DOI
18 Dawson ME. Depyrogenation. Hillerod: Incoporated Press; 1993.
19 Rietschel ET, Brade H. Bacterial endotoxins. Sci Am. 1992; 267(2): 54-61.
20 Simpson JL, Brooks C, Douwes J. Innate immunity in asthma. Pediatr Respir Rev. 2008; 9: 263-270.   DOI
21 Heumann D, Roger T. Initial responses to endotoxins and Gram-negative bacteria. Clin Chim Acta. 2002; 323(1-2): 59-72.   DOI
22 Beutler B, Rietschel ET. Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol. 2003; 3(2): 169-176.   DOI   ScienceOn
23 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.
24 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.   DOI
25 Park BS, Lee JO. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med. 2013; 45: e66, doi:10.1038/emm.2013.97.   DOI
26 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.
27 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.   DOI
28 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.   DOI
29 Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008; 42(2): 145-151.   DOI   ScienceOn
30 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.   DOI
31 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.   DOI   ScienceOn
32 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.   DOI
33 Reed CE, Milton DK. Endotoxin-stimulated innate immunity: A contributing factor for asthma. J Allergy Clin Immunol. 2001; 108(2): 157-166.   DOI   ScienceOn
34 Rylander R. Endotoxin in the environment--exposure and effects. J Endotoxin Res. 2002; 8(4): 241-252.
35 Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nature Rev Genet. 2012; 13(4): 260-270.
36 Pflughoeft KJ, Versalovic J. Human microbiome in health and disease. Annu Rev Pathol. 2012; 7: 99-122.   DOI
37 Alexander C, Rietschel ET. Bacterial lipopolysac-charides and innate immunity. J Endotoxin Res. 2001; 7(3): 167-202.
38 Gioannini TL, Weiss JP. Regulation of interactions of Gram-negative bacterial endotoxins with mammalian cells. Immunol Res. 2007; 39(1-3): 249-260.   DOI
39 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.   DOI
40 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.   DOI
41 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.
42 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.   DOI
43 Bang FB. Rules and regulations regarding serendipity. Prog Clin Biol Res. 1982; 93: 1-5.
44 Cohen E, Bang F, Levin J. Biomedical applications of the horseshoe crab (Limulidae). New York: The University of Michigan Press; 1979.
45 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.   DOI   ScienceOn
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 Thorn J, Rylander R. Inflammatory response after inhalation of bacterial endotoxin assessed by the induced sputum technique. Thorax. 1998; 53(12): 1047-1052.   DOI
50 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.   DOI
51 Rylander R, Haglind P. Airborne endotoxins and humidifier disease. Clin Allergy. 1984; 14: 109-112.   DOI
52 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.
53 Dutch Expert Committee on Occupational Safety. Endotoxins: Health-based recommended occupational exposure limit. Netherland: The Health Council of the Netherlands Press; 2010.
54 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.   DOI   ScienceOn
55 The Unitied States Pharmacopeial Convention. <85> Bacterial endotoxins test. USA: The United States Pharmacopeial Convention Press; 2011.
56 Novitsky TJ. Endotoxins Facts and Fiction: Endotoxin as a component of the bacterial cell. USA: Associates of Cape Cod Press; 1998.
57 Dawson M. Interference with the LAL test and how to address it. USA: Associates of Cape Cod Press; 2005.
58 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.   DOI
59 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.   DOI   ScienceOn
60 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.   DOI
61 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.
62 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.   DOI
63 Institute of Medicine CotAoAaIA. Clearing the air: Asthma and indoor air exposures. Washington D.C: National Academies Press; 2000.
64 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.   DOI
65 Douwes J, Gibson P, Pekkanen J, Pearce N. Noneosinophilic asthma: importance and possible mechanisms. Thorax. 2002; 57(7): 643-648.   DOI   ScienceOn
66 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.   DOI
67 Park JH, Cox-Ganser JM. Mold exposure and respiratory health in damp indoor environments. Front Biosci (Elite Edition). 2011; 3: 757-771.   DOI
68 Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012; 18(5): 673-683.   DOI
69 Pearce N, Pekkanen J, Beasley R. How much asthma is really attributable to atopy?. Thorax. 1999; 54(3): 268-272.   DOI   ScienceOn
70 Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989; 299(6710): 1259-1260.   DOI   ScienceOn
71 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.   DOI
72 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.   DOI   ScienceOn
73 Kiley JP, Caler EV. The lung microbiome. A new frontier in pulmonary medicine. Ann Am Thorac Soc. 2014; 11 (Suppl 1): S66-S70.   DOI
74 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.   DOI   ScienceOn
75 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.   DOI   ScienceOn
76 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.   DOI   ScienceOn
77 Martinez FD. CD14, endotoxin, and asthma risk: actions and interactions. Proc Am Thorac Soc. 2007; 4(3): 221-225.   DOI   ScienceOn
78 Koppelman GH, Postma DS. The genetics of CD14 in allergic disease. Curr Opin Allergy Clin Immunol. 2003; 3(5): 347-352.   DOI
79 Martinez FD, Holt PG. Role of microbial burden in aetiology of allergy and asthma. Lancet. 1999; 354(Suppl 2): SII12-SII15.   DOI
80 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.   DOI
81 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.   DOI
82 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.   DOI   ScienceOn
83 Novitsky TJ. LAL: Discovery and commercial development. USA: Associates of Cape Cod, Incorporated Press; 1996.
84 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.
85 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   DOI
86 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.
87 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.   DOI
88 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.