| Title |
New interplay between interstitial and alveolar macrophages explains pulmonary alveolar proteinosis (PAP) induced by indium tin oxide particles
|
|---|---|
| Published in |
Archives of Toxicology, February 2018
|
| DOI | 10.1007/s00204-018-2168-1 |
| Pubmed ID | |
| Authors |
François Huaux, Valentin De Gussem, Astrid Lebrun, Yousof Yakoub, Mihaly Palmai-Pallag, Saloua Ibouraadaten, Francine Uwambayinema, Dominique Lison |
| Abstract |
Occupational exposure to indium tin oxide (ITO) particles has been associated with the development of severe lung diseases, including pulmonary alveolar proteinosis (PAP). The mechanisms of this lung toxicity remain unknown. Here, we reveal the respective roles of resident alveolar (Siglec-FhighAM) and recruited interstitial (Siglec-FlowIM) macrophages contributing in concert to the development of PAP. In mice treated with ITO particles, PAP is specifically associated with IL-1α (not GM-CSF) deficiency and Siglec-FhighAM (not Siglec-FlowIM) depletion. Mechanistically, ITO particles are preferentially phagocytosed and dissolved to soluble In3+by Siglec-FlowIM. In contrast, Siglec-FhighAM weakly phagocytose or dissolve ITO particles, but are sensitive to released In3+through the expression of the transferrin receptor-1 (TfR1). Blocking pulmonary Siglec-FlowIM recruitment in CCR2-deficient mice reduces ITO particle dissolution, In3+release, Siglec-FhighAM depletion, and PAP formation. Restoration of IL-1-related Siglec-FhighAM also prevented ITO-induced PAP. We identified a new mechanism of secondary PAP development according to which metal ions released from inhaled particles by phagocytic IM disturb IL-1α-dependent AM self-maintenance and, in turn, alveolar clearance. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 11 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 36% |
| Other | 1 | 9% |
| Student > Doctoral Student | 1 | 9% |
| Student > Master | 1 | 9% |
| Unknown | 4 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Immunology and Microbiology | 3 | 27% |
| Agricultural and Biological Sciences | 2 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 9% |
| Medicine and Dentistry | 1 | 9% |
| Unknown | 4 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 February 2018.
All research outputs
#20,466,701
of 23,025,074 outputs
Outputs from Archives of Toxicology
#2,380
of 2,652 outputs
Outputs of similar age
#291,969
of 330,211 outputs
Outputs of similar age from Archives of Toxicology
#25
of 29 outputs
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