PMID- 32726143 OWN - NLM STAT- MEDLINE DCOM- 20201130 LR - 20201130 IS - 1522-1504 (Electronic) IS - 1040-0605 (Linking) VI - 319 IP - 4 DP - 2020 Oct 1 TI - Cobalt exposure via skin alters lung immune cells and enhances pulmonary responses to cobalt in mice. PG - L641-L651 LID - 10.1152/ajplung.00265.2020 [doi] AB - Cobalt has been associated with allergic contact dermatitis and occupational asthma. However, the link between skin exposure and lung responses to cobalt is currently unknown. We investigated the effect of prior dermal sensitization to cobalt on pulmonary physiological and immunological responses after subsequent challenge with cobalt via the airways. BALB/c mice received epicutaneous applications (25 muL/ear) with 5% CoCl(2*)6H(2)O (Co) or the vehicle (Veh) dimethyl sulfoxide (DMSO) twice; they then received oropharyngeal challenges with 0.05% CoCl(2*)6H(2)O or saline five times, thereby obtaining four groups: Veh/Veh, Co/Veh, Veh/Co, and Co/Co. To detect early respiratory responses noninvasively, we performed sequential in vivo microcomputed tomography (microCT). One day after the last challenge, we assessed airway hyperreactivity (AHR) to methacholine, inflammation in bronchoalveolar lavage (BAL), innate lymphoid cells (ILCs) and dendritic cells (DCs) in the lungs, and serum IgE. Compared with the Veh/Veh group, the Co/Co group showed increased microCT-derived lung response, increased AHR to methacholine, mixed neutrophilic and eosinophilic inflammation, elevated monocyte chemoattractant protein-1 (MCP-1), and elevated keratinocyte chemoattractant (KC) in BAL. Flow cytometry in the Co/Co group demonstrated increased DC, type 1 and type 2 conventional DC (cDC1/cDC2), monocyte-derived DC, increased ILC group 2, and natural cytotoxicity receptor(-)ILC group 3. The Veh/Co group showed only increased AHR to methacholine and elevated MCP-1 in BAL, whereas the Co/Veh group showed increased cDC1 and ILC2 in lung. We conclude that dermal sensitization to cobalt may increase the susceptibility of the lungs to inhaling cobalt. Mechanistically, this enhanced susceptibility involves changes in pulmonary DCs and ILCs. FAU - Tsui, Hung-Chang AU - Tsui HC AUID- ORCID: 0000-0002-0105-5455 AD - Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. FAU - Decaesteker, Tatjana AU - Decaesteker T AD - Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium. FAU - Jonckheere, Anne-Charlotte AU - Jonckheere AC AD - Allergy and Clinical Immunology Research Group, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. FAU - Vande Velde, Greetje AU - Vande Velde G AD - Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. FAU - Cremer, Jonathan AU - Cremer J AD - Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium. FAU - Verbeken, Erik AU - Verbeken E AD - Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. FAU - Hoet, Peter H M AU - Hoet PHM AD - Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. FAU - Nemery, Benoit AU - Nemery B AD - Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. FAU - Vanoirbeek, Jeroen A J AU - Vanoirbeek JAJ AD - Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200729 PL - United States TA - Am J Physiol Lung Cell Mol Physiol JT - American journal of physiology. Lung cellular and molecular physiology JID - 100901229 RN - 0W5ETF9M2K (Methacholine Chloride) RN - 3G0H8C9362 (Cobalt) SB - IM MH - Animals MH - Bronchial Hyperreactivity/*drug therapy/immunology MH - Bronchoalveolar Lavage/methods MH - Bronchoalveolar Lavage Fluid/immunology MH - Cobalt/*pharmacology MH - Disease Models, Animal MH - Inflammation/chemically induced/*drug therapy MH - Lung/drug effects/immunology MH - Lymphocytes/*drug effects/immunology MH - Methacholine Chloride/metabolism MH - Mice, Inbred BALB C OTO - NOTNLM OT - cobalt OT - dendritic cell OT - innate lymphoid cell OT - occupational asthma OT - skin exposure EDAT- 2020/07/30 06:00 MHDA- 2020/12/01 06:00 CRDT- 2020/07/30 06:00 PHST- 2020/07/30 06:00 [pubmed] PHST- 2020/12/01 06:00 [medline] PHST- 2020/07/30 06:00 [entrez] AID - 10.1152/ajplung.00265.2020 [doi] PST - ppublish SO - Am J Physiol Lung Cell Mol Physiol. 2020 Oct 1;319(4):L641-L651. doi: 10.1152/ajplung.00265.2020. Epub 2020 Jul 29.