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Increased proinflammatory mediators leads to Activation, Dendritic Cells
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Covalent Binding of Low Molecular Weight Organic Chemicals to Proteins leads to Sensitisation (Sensitization) of the Respiratory Tract||adjacent||Low||Low||Kristie Sullivan (send email)||Under Development: Contributions and Comments Welcome||Under Development|
Life Stage Applicability
|All life stages||High|
Key Event Relationship Description
The presence of cellular danger signals at the local exposure site leads to the induction and amplification of immune responses in dendritic cells.
Evidence Collection Strategy
Evidence Supporting this KER
DCs express receptors for, and respond to, constitutive and inflammatory chemokines and other chemoattractants, such as platelet-activating factor and formyl peptides. Much investigation has gone into assessing the specific mechanistic events involved in skin sensitizer-caused DC migration. Ex vivo studies with intact human skin, epidermal sheets, and MUTZ-3-derived Langerhans cells (LC) show that fibroblasts mediate migration of cytokine-matured LC via chemokines, including CXCL12, CXCR4, and dermis-derived CCL2 and CCL5. (Ouwehand, et al., 2011)
Uncertainties and Inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Dendritic cell activation is not limited to a specific sex or age.
OUWEHAND K, SPIEKSTRA SW, WAAJIMAN T, SCHEPER RJ, DE GRUJIL TD, GIBBS S. 2011. Technical advance: Langerhans cells derived from a human cell line in a full-thickness skin equivalent undergo allergen-induced maturation and migration. J Leukoc Biol. 290(5):1027-33.
SILVA, A., NUNES, C., MARTINS, J., DINIS, T. C., LOPES, C., NEVES, B. & CRUZ, T. 2014. Respiratory sensitizer hexamethylene diisocyanate inhibits SOD 1 and induces ERK-dependent detoxifying and maturation pathways in dendritic-like cells. Free Radic Biol Med, 72, 238-46.