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Cited by 204Asthma and respiratory diseasesAir Quality and Health ImpactsOccupational exposure and asthma

Pulmonary Exposure to Particles during Pregnancy Causes Increased Neonatal Asthma Susceptibility

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Fedulov, Alexey V., Leme, Adriana, Yang, Zhiping, Dahl, Morten, Lim, Robert, Mariani, Thomas J., Kobzik, Lester·2008·American Journal of Respiratory Cell and Molecular Biology
DOI 10.1165/rcmb.2007-0124ocPMC PMC2176127
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Abstract

Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control "inert" titanium dioxide (TiO(2)) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice (or nonpregnant controls) received particle suspensions intranasally at Day 14 of pregnancy. Lung inflammatory responses were evaluated 48 hours after exposure. Offspring of particle- or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Nonpregnant females had the expected minimal response to "inert" TiO(2). In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO(2) and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO(2). Neonates of mothers exposed to TiO(2) (and DEP, but not PBS) developed AHR and AI, indicating that pregnancy exposure to both "inert" TiO(2) and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles can cause increased allergic susceptibility in offspring.

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  • Pregnant Balb/c mice exhibit an acute inflammatory response to diesel exhaust PM0.1 and titanium dioxide particles, in contrast to non-pregnant females.

    “Fedulov et al. [83] subsequently showed pregnant Balb/c mice exhibit an acute inflammatory response to both diesel exhaust PM0.1 and more “inert” particles, titanium dioxide (TiO2), in contrast to non-pregnant females.”

    From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [83]

    The Results (page not provided) report robust acute lung inflammation after TiO2 in pregnant mice but minimal response in nonpregnant mice. The contrast does not hold for diesel exhaust particles: both groups had significantly increased lung neutrophils after exposure, although pregnant mice had higher serum cytokine levels. Materials and Methods describes the particles as respirable-size but does not specify PM0.1. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Offspring born to mothers exposed to diesel exhaust PM0.1 or titanium dioxide develop airway hyperresponsiveness and airway inflammation following OVA challenge.

    “Offspring born to mothers exposed to either type of particle went on to develop AHR and display airway inflammation following OVA challenge.”

    From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [83]

    The Results report that offspring of DEP-exposed mothers had increased airway hyperresponsiveness and allergic airway inflammation after OVA sensitization and challenge, and that offspring of TiO2-exposed mothers showed the same outcomes. The Materials and Methods describe the DEP as “respirable-size” but do not establish the PM0.1 size specified in the claim. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Models of gestational fine and ultrafine PM exposure confirm intrauterine oxidative damage and inflammation.

    “Models of gestational fine and ultrafine PM exposure confirm intrauterine oxidative damage and inflammation [83, 92].”

    From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [83]

    The Abstract and Discussion report that particle exposure during pregnancy increased inflammation in the mothers’ lungs, and the offspring showed greater allergic susceptibility. They do not establish intrauterine oxidative damage or inflammation: the reported inflammatory response was maternal and pulmonary. The cited passages also do not establish the claim specifically for fine and ultrafine PM. (LLM, conf=0.86)

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Research works printed but not linked: 50

  1. [1]von Mutius E, Schmid S, the PASTURE Study Group. The PASTURE project: EU support for the improvement of knowledge about risk factors and preventive factors for atopy in Europe. Allergy 2006;61:407–413. [DOI] [PubMed] [Google Scholar]
  2. [2]von Mutius E. The burden of childhood asthma. Arch Dis Child 2000;82:II2–II5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. [3]Wills-Karp M. Murine models of asthma in understanding immune dysregulation in human asthma. Immunopharmacology 2000;48:263–268. [DOI] [PubMed] [Google Scholar]
  4. [4]Weiss ST. Epidemiology and heterogeneity of asthma. Annals of Allergy, Asthma, &. Immunology 2001;87:5–8. [DOI] [PubMed] [Google Scholar]
  5. [5]Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995;332:133–138. (see comments). [DOI] [PubMed] [Google Scholar]
  6. [6]Prescott SL. Maternal allergen exposure as a risk factor for childhood asthma. Curr Allergy Asthma Rep 2006;6:75–80. [DOI] [PubMed] [Google Scholar]
  7. [7]Hamada K, Suzaki Y, Goldman A, Ning YY, Goldsmith C, Palecanda A, Coull B, Hubeau C, Kobzik L. Allergen-independent maternal transmission of asthma susceptibility. J Immunol 2003;170:1683–1689. [DOI] [PubMed] [Google Scholar]
  8. [8]Fedulov A, Silverman E, Xiang Y, Leme A, Kobzik L. Immunostimulatory CpG oligonucleotides abrogate allergic susceptibility in a murine model of maternal asthma transmission. J Immunol 2005;175:4292–4300. [DOI] [PubMed] [Google Scholar]
  9. [9]Leme AS, Hubeau C, Xiang Y, Goldman A, Hamada K, Suzaki Y, Kobzik L. Role of breast milk in a mouse model of maternal transmission of asthma susceptibility. J Immunol 2006;176:762–769. [DOI] [PubMed] [Google Scholar]
  10. [10]Goldsmith C, Kobzik L. Particulate air pollution and asthma: a review of the epidemiological and biological studies. Rev Environ Health 1999;14:121–134. [DOI] [PubMed] [Google Scholar]
  11. [11]von Mutius E, Martinez FD, Fritzsch C, Nicolai T, Roell G, Thiemann HH. Prevalence of asthma and atopy in two areas of West and East Germany. Am J Respir Crit Care Med 1994;149:358–364. [DOI] [PubMed] [Google Scholar]
  12. [12]Venn AJ, Lewis SA, Cooper M, Hubbard R, Britton J. Living near a main road and the risk of wheezing illness in children. Am J Respir Crit Care Med 2001;164:2177–2180. [DOI] [PubMed] [Google Scholar]
  13. [13]Miyake Y, Yura A, Iki M. Relationship between distance from major roads and adolescent health in Japan. J Epidemiol 2002;12:418–423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. [14]Takano H, Ichinose T, Miyabara Y, Yoshikawa T, Sagai M. Diesel exhaust particles enhance airway responsiveness following allergen exposure in mice. Immunopharmacol Immunotoxicol 1998;20:329–336. [DOI] [PubMed] [Google Scholar]
  15. [15]Miyabara Y, Takano H, Ichinose T, Lim HB, Sagai M. Diesel exhaust enhances allergic airway inflammation and hyperresponsiveness in mice. Am J Respir Crit Care Med 1998;157:1138–1144. [DOI] [PubMed] [Google Scholar]
  16. [16]Diaz-Sanchez D, Tsien A, Fleming J, Saxon A. Combined diesel exhaust particulate and ragweed allergen challenge markedly enchance human in vivo nasal ragweed-specific IgE and skews cytokine production to a T-helper cell 2-type pattern. J Immunol 1997;158:2406–2413. [PubMed] [Google Scholar]
  17. [17]Fujimaki H, Saneyoshi K, Shiraishi F, Imai T, Endo T. Inhalation of diesel exhaust enhances antigen-specific IgE antibody production in mice. Toxicology 1997;116:227–233. [DOI] [PubMed] [Google Scholar]
  18. [18]Suzuki T, Kanoh T, Kanbayashi M, Todome Y, Ohkuni H. The adjuvant activity of pyrene in diesel exhaust on IgE antibody production in mice. Arerugi 1993;42:963–968. [PubMed] [Google Scholar]
  19. [19]Pauwels RA, Brusselle GG, Tournoy KG, Lambrecht BN, Kips JC. Cytokines and their receptors as therapeutic targets in asthma. Clin Exp Allergy 1998;28:1–5. [PubMed] [Google Scholar]
  20. [20]Cohn L, Herrick C, Niu N, Homer R, Bottomly K. IL-4 promotes airway eosinophilia by suppressing IFN-gamma production: defining a novel role for IFN-gamma in the regulation of allergic airway inflammation. J Immunol 2001;166:2760–2767. [DOI] [PubMed] [Google Scholar]
  21. [21]Southam DS, Dolovich M, O'Byrne PM, Inman M. D. Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia. Am J Physiol Lung Cell Mol Physiol 2002;282:L833–L839. [DOI] [PubMed] [Google Scholar]
  22. [22]Hamada K, Suzaki Y, Leme A, Ito T, Myamoto K, Kobzik L, Kimura H. Exposure of pregnant mice to an air pollutant aerosol increases asthma susceptibility in offspring. J Toxicol Environ Health 2006; (In Press). [DOI] [PubMed]
  23. [23]Adler A, Cieslewicz G, Irvin CG. Unrestrained plethysmography is an unreliable measure of airway responsiveness in BALB/c and C57BL/6 mice. J Appl Physiol 2004;97:286–292. [DOI] [PubMed] [Google Scholar]
  24. [24]Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen G, Irvin C, Gelfand E. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med 1997;156:766–775. [DOI] [PubMed] [Google Scholar]
  25. [25]Lutchen KR, Yang K, Kaczka DW, Suki B. Optimal ventilation waveforms for estimating low-frequency respiratory impedance. J Appl Physiol 1993;75:478–488. [DOI] [PubMed] [Google Scholar]
  26. [26]Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ. Input impedance and peripheral inhomogeneity of dog lungs. J Appl Physiol 1992;72:168–178. [DOI] [PubMed] [Google Scholar]
  27. [28]Dohi M, Tsukamoto S, Nagahori T, Shinagawa K, Saitoh K, Tanaka Y, Kobayashi S, Tanaka R, To Y, Yamamoto K. Noninvasive system for evaluating the allergen-specific airway response in a murine model of asthma. Lab Invest 1999;79:1559–1571. [PubMed] [Google Scholar]
  28. [29]Gomes R, Shen X, Ramchandani R, Tepper RS, Bates JHT. Comparative respiratory system mechanics in rodents. J Appl Physiol 2000;89:908–916. [DOI] [PubMed] [Google Scholar]
  29. [30]Bommel H, Li-Weber M, Serfling E, Duschl A. The environmental pollutant pyrene induces the production of IL-4. J Allergy Clin Immunol 2000;105:796–802. [DOI] [PubMed] [Google Scholar]
  30. [31]Warheit DB, Brock WJ, Lee KP, Webb TR, Reed KL. Comparative pulmonary toxicity inhalation and instillation studies with different TiO2 particle formulations: impact of surface treatments on particle toxicity. Toxicol Sci 2005;88:514–524. [DOI] [PubMed] [Google Scholar]
  31. [32]Renwick LC, Brown D, Clouter A, Donaldson K. Increased inflammation and altered macrophage chemotactic responses caused by two ultrafine particle types. Occup Environ Med 2004;61:442–447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. [33]Drumm K, Schindler H, Buhl R, Kustner E, Smolarski R, Kienast K. Indoor air pollutants stimulate interleukin-8-specific mRNA expression and protein secretion of alveolar macrophages. Lung 1999;177:9–19. [DOI] [PubMed] [Google Scholar]
  33. [34]Ahn MH, Kang CM, Park CS, Park SJ, Rhim T, Yoon PO, Chang HS, Kim SH, Kyono H, Kim KC. Titanium dioxide particle-induced goblet cell hyperplasia: association with mast cells and IL-13. Respir Res 2005;6:34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. [35]Kang CM, Jang AS, Ahn MH, Shin JA, Kim JH, Choi YS, Rhim TY, Park CS. Interleukin-25 and interleukin-13 production by alveolar macrophages in response to particles. Am J Respir Cell Mol Biol 2005;33:290–296. [DOI] [PubMed] [Google Scholar]
  35. [36]van Zijverden M, van der Pijl A, Bol M, van Pinxteren FA, de Haar C, Penninks AH, van Loveren H, Pieters R. Diesel exhaust, carbon black, and silica particles display distinct Th1/Th2 modulating activity. Toxicol Appl Pharmacol 2000;168:131–139. [DOI] [PubMed] [Google Scholar]
  36. [37]Huffman LJ, Frazer DG, Prugh D, Brumbaugh K, Platania C, Reynolds JS, Goldsmith WT. Enhanced pulmonary inflammatory response to inhaled endotoxin in pregnant rats. J Toxicol Environ Health A 2004;67:125–144. [DOI] [PubMed] [Google Scholar]
  37. [38]Gunnison AF, Weideman PA, Sobo M. Enhanced inflammatory response to acute ozone exposure in rats during pregnancy and lactation. Fundam Appl Toxicol 1992;19:607–612. [DOI] [PubMed] [Google Scholar]
  38. [39]Lin H, Mosmann TR, Guilbert L, Tuntipopipat S, Wegmann TG. Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol 1993;151:4562–4573. [PubMed] [Google Scholar]
  39. [41]Albrecht ED, Aberdeen GW, Pepe GJ. The role of estrogen in the maintenance of primate pregnancy. Am J Obstet Gynecol 2000;182:432–438. [DOI] [PubMed] [Google Scholar]
  40. [43]Arredondo F, Noble LS. Endocrinology of recurrent pregnancy loss. Semin Reprod Med 2006;24:33–39. [DOI] [PubMed] [Google Scholar]
  41. [44]Piccinni MP, Scaletti C, Maggi E, Romagnani S. Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J Neuroimmunol 2000;109:30–33. [DOI] [PubMed] [Google Scholar]
  42. [45]Chao TC, Phuangsab A, Van Alten PJ, Walter RJ. Steroid sex hormones and macrophage function: regulation of chemiluminescence and phagocytosis. Am J Reprod Immunol 1996;35:106–113. [DOI] [PubMed] [Google Scholar]
  43. [46]Chao TC, Van Alten PJ, Walter RJ. Steroid sex hormones and macrophage function: modulation of reactive oxygen intermediates and nitrite release. Am J Reprod Immunol 1994;32:43–52. [DOI] [PubMed] [Google Scholar]
  44. [47]Chao TC, Van Alten PJ, Greager JA, Walter RJ. Steroid sex hormones regulate the release of tumor necrosis factor by macrophages. Cell Immunol 1995;160:43–49. [DOI] [PubMed] [Google Scholar]
  45. [48]Chao TC, Chao HH, Chen MF, Greager JA, Walter RJ. Female sex hormones modulate the function of LPS-treated macrophages. Am J Reprod Immunol 2000;44:310–318. [DOI] [PubMed] [Google Scholar]
  46. [49]Wieser F, Hosmann J, Tschugguel W, Czerwenka K, Sedivy R, Huber JC. Progesterone increases the number of Langerhans cells in human vaginal epithelium. Fertil Steril 2001;75:1234–1235. [DOI] [PubMed] [Google Scholar]
  47. [50]Ivanova E, Kyurkchiev D, Altankova I, Dimitrov J, Binakova E, Kyurkchiev S. CD83 monocyte-derived dendritic cells are present in human decidua and progesterone induces their differentiation in vitro. Am J Reprod Immunol 2005;53:199–205. [DOI] [PubMed] [Google Scholar]
  48. [51]Mao A, Paharkova-Vatchkova V, Hardy J, Miller MM, Kovats S. Estrogen selectively promotes the differentiation of dendritic cells with characteristics of Langerhans cells. J Immunol 2005;175:5146–5151. [DOI] [PubMed] [Google Scholar]
  49. [52]Hubeau C, Apostolou I, Kobzik L. Adoptively transferred allergen-specific T cells cause maternal transmission of asthma risk. Am J Pathol 2006;168:1931–1939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. [53]Baron RM, Carvajal IM, Fredenburgh LE, Liu X, Porrata Y, Cullivan ML, Haley KJ, Sonna LA, De Sanctis GT, Ingenito EP, et al. Nitric oxide synthase-2 down-regulates surfactant protein-B expression and enhances endotoxin-induced lung injury in mice. FASEB J 2004;18:1276–1278. [DOI] [PubMed] [Google Scholar]

Cited by

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Authors
Fedulov, A. V., Leme, A., Yang, Z., Dahl, M., Lim, R., Mariani, T. J., & Kobzik, L.
Affiliations
  • Harvard University (US)
  • Brigham and Women's Hospital (US)
ORCID
Venue
American Journal of Respiratory Cell and Molecular Biology
Publisher
Oxford University Press (OUP)
Published
2008-01-01
Volume
38
Issue
1
Pages
57-67
ISSN
  • 1044-1549 (ISSN-L)
  • 1535-4989
DOI
10.1165/rcmb.2007-0124oc
PMC
PMC2176127
OpenAlex
W2041674455
Cited by
204
References
1
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FWCI
7.83
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL69760, R01HL069760)
Topics
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
Keywords
maternal air pollution exposure, diesel exhaust particles, titanium dioxide particles, pregnancy, airway hyperresponsiveness, allergic airway inflammation, ovalbumin sensitization, lung inflammation, fetal programming, maternal immune response, gene expression profiling
MeSH terms
Air Pollutants, Animals, Asthma, Vehicle Emissions, Female, Gene Expression Regulation, Humans, Immunity, Maternally-Acquired, Lung, Maternal-Fetal Exchange, Pregnancy, Titanium, Cytokines, Maternal Exposure, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Particulate Matter

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