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. 2001 Nov;56(11):823–826. doi: 10.1136/thorax.56.11.823

Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge

F Jahnsen 1, E Moloney 1, T Hogan 1, J Upham 1, C Burke 1, P Holt 1
PMCID: PMC1745967  PMID: 11641504

Abstract

BACKGROUND—Airway dendritic cells (DC) play an important role in chronic allergic airway inflammation in experimental animals, but a similar role for DC in human allergic asthma has been difficult to define. This pilot study was undertaken to elucidate the role of DC in allergic asthma by examining their potential to migrate to the lower airways in response to bronchial challenge with specific allergen.
METHODS—Bronchial biopsy specimens were obtained from seven patients with allergic asthma before and 4-5 hours after allergen challenge. Multicolour immunofluorescence staining was performed on mucosal cryosections to identify changes in the number and phenotypes of DC.
RESULTS—A dramatic increase in the number of CD1c+HLA-DR+ DC were observed in the lamina propria after challenge compared with baseline (22.4 v 7.8 cells/mm2). The rapid accumulation (within 4-5 hours) of these cells strongly suggests that they were directly recruited from peripheral blood.
CONCLUSION—We have shown for the first time that a specific DC subset rapidly emigrates into the human bronchial mucosa during allergic inflammation. While this study is based on relatively few patients, the consistency of the overall results strongly suggests that the rapid population dynamics of human airway DC closely parallel those in animal models of acute inflammation. These findings support suggestions that DC have an important role in human airway allergy.



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Selected References

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  1. Burke C. M., Sreenan S., Pathmakanthan S., Patterson J., Schmekel B., Poulter L. W. Relative effects of inhaled corticosteroids on immunopathology and physiology in asthma: a controlled study. Thorax. 1996 Oct;51(10):993–999. doi: 10.1136/thx.51.10.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dzionek A., Fuchs A., Schmidt P., Cremer S., Zysk M., Miltenyi S., Buck D. W., Schmitz J. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol. 2000 Dec 1;165(11):6037–6046. doi: 10.4049/jimmunol.165.11.6037. [DOI] [PubMed] [Google Scholar]
  3. Evans D. J., Barnes P. J., Cluzel M., O'Connor B. J. Effects of a potent platelet-activating factor antagonist, SR27417A, on allergen-induced asthmatic responses. Am J Respir Crit Care Med. 1997 Jul;156(1):11–16. doi: 10.1164/ajrccm.156.1.9611112. [DOI] [PubMed] [Google Scholar]
  4. Holt P. G., Oliver J., Bilyk N., McMenamin C., McMenamin P. G., Kraal G., Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med. 1993 Feb 1;177(2):397–407. doi: 10.1084/jem.177.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Holt P. G., Schon-Hegrad M. A., Phillips M. J., McMenamin P. G. Ia-positive dendritic cells form a tightly meshed network within the human airway epithelium. Clin Exp Allergy. 1989 Nov;19(6):597–601. doi: 10.1111/j.1365-2222.1989.tb02752.x. [DOI] [PubMed] [Google Scholar]
  6. Hoogsteden H. C., Verhoeven G. T., Lambrecht B. N., Prins J. B. Airway inflammation in asthma and chronic obstructive pulmonary disease with special emphasis on the antigen-presenting dendritic cell: influence of treatment with fluticasone propionate. Clin Exp Allergy. 1999 Jun;29 (Suppl 2):116–124. doi: 10.1046/j.1365-2222.1999.00020.x. [DOI] [PubMed] [Google Scholar]
  7. Jahnsen F. L., Haraldsen G., Aanesen J. P., Haye R., Brandtzaeg P. Eosinophil infiltration is related to increased expression of vascular cell adhesion molecule-1 in nasal polyps. Am J Respir Cell Mol Biol. 1995 Jun;12(6):624–632. doi: 10.1165/ajrcmb.12.6.7539273. [DOI] [PubMed] [Google Scholar]
  8. Jahnsen F. L., Lund-Johansen F., Dunne J. F., Farkas L., Haye R., Brandtzaeg P. Experimentally induced recruitment of plasmacytoid (CD123high) dendritic cells in human nasal allergy. J Immunol. 2000 Oct 1;165(7):4062–4068. doi: 10.4049/jimmunol.165.7.4062. [DOI] [PubMed] [Google Scholar]
  9. Kohrgruber N., Halanek N., Gröger M., Winter D., Rappersberger K., Schmitt-Egenolf M., Stingl G., Maurer D. Survival, maturation, and function of CD11c- and CD11c+ peripheral blood dendritic cells are differentially regulated by cytokines. J Immunol. 1999 Sep 15;163(6):3250–3259. [PubMed] [Google Scholar]
  10. Lambrecht B. N., Salomon B., Klatzmann D., Pauwels R. A. Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol. 1998 Apr 15;160(8):4090–4097. [PubMed] [Google Scholar]
  11. McWilliam A. S., Napoli S., Marsh A. M., Pemper F. L., Nelson D. J., Pimm C. L., Stumbles P. A., Wells T. N., Holt P. G. Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli. J Exp Med. 1996 Dec 1;184(6):2429–2432. doi: 10.1084/jem.184.6.2429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Möller G. M., Overbeek S. E., Van Helden-Meeuwsen C. G., Van Haarst J. M., Prens E. P., Mulder P. G., Postma D. S., Hoogsteden H. C. Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clin Exp Allergy. 1996 May;26(5):517–524. [PubMed] [Google Scholar]
  13. Nelson D. J., McWilliam A. S., Haining S., Holt P. G. Modulation of airway intraepithelial dendritic cells following exposure to steroids. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):475–481. doi: 10.1164/ajrccm.151.2.7842209. [DOI] [PubMed] [Google Scholar]
  14. Stumbles P. A., Thomas J. A., Pimm C. L., Lee P. T., Venaille T. J., Proksch S., Holt P. G. Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity. J Exp Med. 1998 Dec 7;188(11):2019–2031. doi: 10.1084/jem.188.11.2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Xia W., Pinto C. E., Kradin R. L. The antigen-presenting activities of Ia+ dendritic cells shift dynamically from lung to lymph node after an airway challenge with soluble antigen. J Exp Med. 1995 Apr 1;181(4):1275–1283. doi: 10.1084/jem.181.4.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]

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