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Key Event Title
Systemic acute phase response
|Level of Biological Organization|
Key Event Components
|acute-phase response||Acute phase proteins||increased|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Interaction with lung cells leading to atherosclerosis||KeyEvent||Ulla Vogel (send email)||Under development: Not open for comment. Do not cite||Under Development|
|All life stages||High|
Key Event Description
During acute phase response, the plasma concentration of acute phase proteins (APP) changes in more than 25%. APPs that increase their concentration during APR are called positive APP, while negative APP are decreased during APR 1. In humans, positive APPs include C-reactive protein, serum amyloid A, C3 and C4 complement system, mannose-binding lectin, fibrinogen, fibronectin, ferritin, haptoglobin, hemopexin, among others 1,2. In humans the two major APPs are C-reactive protein (CRP) and serum amyloid A (SAA), whose concentration can increase in more than 1000-fold during acute phase response 1. SAA and CRP have been shown to be correlated in humans 3-5.In mice, the major APP are serum amyloid A, haptoglobin and serum amyloid P6.
How It Is Measured or Detected
Systemic acute phase response is assessed by measuring APPs concentrations in blood plasma or serum, most often CRP and SAA. In humans, these proteins are measured by immunoassays detecting single or multiple proteins 4,7-12. In addition, CRP is measured by turbidimetric 13-15 and nephelometric assays 16.
In mice, CRP is not a major APP 6, therefore SAA isoforms are measured using ELISA assays or western blot 17-21.
Domain of Applicability
- Taxonomic applicability: APR is part of the immune response and is observed in vertebrates6.
- Life stages applicability: This key event is applicable to all life stages.
- Sex applicability: This key event is applicable to male and females sexes.
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7 Meier, R. et al. Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers. Environ Health Perspect 122, 726-732, doi:10.1289/ehp.1307100 (2014).
8 Baumann, R. et al. Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes. J Expo Sci Environ Epidemiol 28, 84-91, doi:10.1038/jes.2016.86 (2018).
9 Adetona, A. M. et al. Impact of Work Task-Related Acute Occupational Smoke Exposures on Select Proinflammatory Immune Parameters in Wildland Firefighters. J Occup Environ Med 59, 679-690, doi:10.1097/JOM.0000000000001053 (2017).
10 Andersen, M. H. G. et al. Health effects of exposure to diesel exhaust in diesel-powered trains. Part Fibre Toxicol 16, 21, doi:10.1186/s12989-019-0306-4 (2019).
11 Walker, E. S. et al. Acute differences in blood lipids and inflammatory biomarkers following controlled exposures to cookstove air pollution in the STOVES study. Int J Environ Health Res 32, 565-578, doi:10.1080/09603123.2020.1785402 (2022).
12 Wyatt, L. H., Devlin, R. B., Rappold, A. G., Case, M. W. & Diaz-Sanchez, D. Low levels of fine particulate matter increase vascular damage and reduce pulmonary function in young healthy adults. Part Fibre Toxicol 17, 58, doi:10.1186/s12989-020-00389-5 (2020).
13 Kim, J. Y., Chen, J. C., Boyce, P. D. & Christiani, D. C. Exposure to welding fumes is associated with acute systemic inflammatory responses. Occup Environ Med 62, 157-163, doi:10.1136/oem.2004.014795 (2005).
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16 Brand, P. et al. Relationship between welding fume concentration and systemic inflammation after controlled exposure of human subjects with welding fumes from metal inert gas brazing of zinc-coated materials. J Occup Environ Med 56, 1-5, doi:10.1097/JOM.0000000000000061 (2014).
17 Hadrup, N. et al. Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice. Nanotoxicology 13, 1275-1292, doi:10.1080/17435390.2019.1654004 (2019).
18 Poulsen, S. S. et al. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice. PLoS One 12, e0174167, doi:10.1371/journal.pone.0174167 (2017).
19 Gutierrez, C. T. et al. Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in mice. Part Fibre Toxicol 20, 4, doi:10.1186/s12989-023-00514-0 (2023).
20 Christophersen, D. V. et al. Accelerated atherosclerosis caused by serum amyloid A response in lungs of ApoE(-/-) mice. FASEB J 35, e21307, doi:10.1096/fj.202002017R (2021).
21 Halappanavar, S. et al. Pulmonary response to surface-coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: a toxicogenomic study. Environ Mol Mutagen 52, 425-439, doi:10.1002/em.20639 (2011).