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Inhalation of alkyl...
Inhalation of alkylating mustard causes long-term T cell-dependent inflammation in airways and growth of connective tissue
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- Ekstrand-Hammarström, Barbro (författare)
- Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden
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- Wigenstam, Elisabeth, 1980- (författare)
- Umeå universitet,Lungmedicin,Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden
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- Bucht, Anders (författare)
- Umeå universitet,Lungmedicin,Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden
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(creator_code:org_t)
- Elsevier, 2011
- 2011
- Engelska.
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Ingår i: Toxicology. - : Elsevier. - 0300-483X .- 1879-3185. ; 280:3, s. 88-97
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Low-dose exposure of alkylating mustard gas causes long-term respiratory complications characterized by bronchitis and lung fibrosis. In this study, we utilized a mouse model for lung exposure of the nitrogen mustard melphalan, in order to define early and late events in the pathogenesis such as expression of pro-inflammatory cytokines, recruitment of inflammatory cells to airways and late-phase fibrosis. We investigated the roles of different T lymphocyte subsets on the inflammatory response by using knockout mice lacking either the genes expressing T cell receptor (TCR)αβ or TCRγδ, and compared the responsiveness with that of wild type mice and double knockout mice completely deficient in T cells. Exposure to melphalan induced an early burst of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and IL-23 in airways, followed by extensive infiltration of neutrophils in the lung tissue and airways within 24h. The acute phase was followed by a sustained lymphocytic response that persisted for at least 14 days with resulting lung fibrosis. Engagement of T lymphocytes, particularly the γδ T cell subset, was crucial both for the acute cytokine and neutrophil response and for the late-phase lung fibrosis as indicated by the lack of response in γδ T cell deficient mice. Our data demonstrate that T lymphocytes play a prominent role in the pathogenesis of long-term lung injuries caused by strong alkylating agents.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Nyckelord
- Alkylating mustard
- T lymphocytes
- γδ T cells
- Airway inflammation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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