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Event: 1439
Key Event Title
Systemic acute phase response
Short name
Biological Context
Level of Biological Organization |
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Organ |
Organ term
Organ term |
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blood |
Key Event Components
Process | Object | Action |
---|---|---|
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 Do not cite | Under Development |
Taxonomic Applicability
Life Stages
Life stage | Evidence |
---|---|
All life stages | High |
Sex Applicability
Term | Evidence |
---|---|
Male | High |
Female | High |
Key Event Description
Acute phase response (APR) is the systemic response to acute and chronic inflammatory states, for example bacterial infection, trauma and infarction. These changes include variations in plasma concentration of proteins, along with other physiological changes. Proteins are considered acute phase proteins (APPs) when their plasma concentration changes at least 25% (Gabay & Kushner, 1999).
APPs that increase their concentration during APR are called positive APP, while negative APP are decreased during APR (Gabay & Kushner, 1999). In humans, the two major APPs are C-reactive protein (CRP) and serum amyloid A (SAA), whose concentration can increase more than 1000-fold during an acute phase response (Gabay & Kushner, 1999). In mice, the major APPs (i.e. the APPs whose plasma concentration increases the most during APR) are SAA, haptoglobin and serum amyloid P (Cray, Zaias, & Altman, 2009).
How It Is Measured or Detected
Systemic acute phase response is assessed by measuring acute phase proteins (APPs) concentrations in blood plasma or serum.
In mice, serum amyloid A (SAA) isoforms are measured using enzyme-linked immunosorbent assay (ELISA) assays or Western blot. (Christophersen et al., 2021; Gutierrez et al., 2023; Hadrup et al., 2019; Halappanavar et al., 2011; Poulsen et al., 2017). ELISA assays allows the measurement of proteins in a sample by adsorbing the desired proteins (antigens) to an inert surface. Using antibodies specific to the protein and an enzyme that catalyzes the reaction, a colorimetric signal is produced and measured (Nelson, Nelson, Lehninger, & Cox, 2017). In the case of Western blot, also called immunoblot assay, proteins in a sample are first separated by gel electrophoresis. Following, the proteins are transferred to a membrane and treated with antibodies, obtaining a coloured precipitate along the band of the desired protein (Nelson et al., 2017).
In humans, most often C-reactive protein (CRP) and SAA are measured. These proteins are measured by immunoassays detecting single or multiple proteins (Adetona et al., 2017; Andersen et al., 2019; Baumann et al., 2018; Meier et al., 2014; Monse et al., 2018; Walker et al., 2022; Wyatt, Devlin, Rappold, Case, & Diaz-Sanchez, 2020). In addition, CRP is measured by turbidimetric (Barregard et al., 2006; Kim, Chen, Boyce, & Christiani, 2005; Sikkeland et al., 2018) and nephelometric assays (Brand et al., 2014).
For both techniques, a blood sample (serum or plasma) is mixed with a suspension of latex beads coated with CRP antibodies. When CRP binds to the beads, a complex is formed that produces the scattering of light. The amount of light scattered is proportional to the amount of complexes formed. While in nephelometry the amount of light scaterred is measure, in turbidimetry the amount of light that passes through the suspension is measured. The measurements are later converted to CRP concentration using a calibration curve (Drieghe, Alsaadi, Tugirimana, & Delanghe, 2014; Hamilton, 2014).
CRP is used in the clinical setting as a marker of systemic inflammation.
Domain of Applicability
- Taxonomic applicability: Acute phase response is part of the immune response and is observed in vertebrates (Cray et al., 2009).
- Life stages applicability: This key event is applicable to all life stages.
- Sex applicability: This key event is applicable to male and females sexes.
References
Adetona, A. M., Adetona, O., Gogal, R. M., Jr., Diaz-Sanchez, D., Rathbun, S. L., & Naeher, L. P. (2017). Impact of Work Task-Related Acute Occupational Smoke Exposures on Select Proinflammatory Immune Parameters in Wildland Firefighters. J Occup Environ Med, 59(7), 679-690. doi:10.1097/JOM.0000000000001053
Andersen, M. H. G., Frederiksen, M., Saber, A. T., Wils, R. S., Fonseca, A. S., Koponen, I. K., . . . Vogel, U. (2019). Health effects of exposure to diesel exhaust in diesel-powered trains. Part Fibre Toxicol, 16(1), 21. doi:10.1186/s12989-019-0306-4
Barregard, L., Sallsten, G., Gustafson, P., Andersson, L., Johansson, L., Basu, S., & Stigendal, L. (2006). Experimental exposure to wood-smoke particles in healthy humans: effects on markers of inflammation, coagulation, and lipid peroxidation. Inhal Toxicol, 18(11), 845-853. doi:10.1080/08958370600685798
Baumann, R., Gube, M., Markert, A., Davatgarbenam, S., Kossack, V., Gerhards, B., . . . Brand, P. (2018). Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes. J Expo Sci Environ Epidemiol, 28(1), 84-91. doi:10.1038/jes.2016.86
Brand, P., Bauer, M., Gube, M., Lenz, K., Reisgen, U., Spiegel-Ciobanu, V. E., & Kraus, T. (2014). 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), 1-5. doi:10.1097/JOM.0000000000000061
Christophersen, D. V., Moller, P., Thomsen, M. B., Lykkesfeldt, J., Loft, S., Wallin, H., . . . Jacobsen, N. R. (2021). Accelerated atherosclerosis caused by serum amyloid A response in lungs of ApoE(-/-) mice. FASEB J, 35(3), e21307. doi:10.1096/fj.202002017R
Cray, C., Zaias, J., & Altman, N. H. (2009). Acute phase response in animals: a review. Comp Med, 59(6), 517-526.
Drieghe, S. A., Alsaadi, H., Tugirimana, P. L., & Delanghe, J. R. (2014). A new high-sensitive nephelometric method for assaying serum C-reactive protein based on phosphocholine interaction. Clinical chemistry and laboratory medicine, 52(6), 861-867. doi:10.1515/cclm-2013-0669
Gabay, C., & Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. N Engl J Med, 340(6), 448-454. doi:10.1056/NEJM199902113400607
Gutierrez, C. T., Loizides, C., Hafez, I., Brostrom, A., Wolff, H., Szarek, J., . . . Vogel, U. (2023). Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in mice. Part Fibre Toxicol, 20(1), 4. doi:10.1186/s12989-023-00514-0
Hadrup, N., Rahmani, F., Jacobsen, N. R., Saber, A. T., Jackson, P., Bengtson, S., . . . Vogel, U. (2019). Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice. Nanotoxicology, 13(9), 1275-1292. doi:10.1080/17435390.2019.1654004
Halappanavar, S., Jackson, P., Williams, A., Jensen, K. A., Hougaard, K. S., Vogel, U., . . . Wallin, H. (2011). 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(6), 425-439. doi:10.1002/em.20639
Hamilton, R. G. (2014). Methods (In Vitro and In Vivo): Nephelometry and Turbidimetry. In Encyclopedia of Medical Immunology.
Kim, J. Y., Chen, J. C., Boyce, P. D., & Christiani, D. C. (2005). Exposure to welding fumes is associated with acute systemic inflammatory responses. Occup Environ Med, 62(3), 157-163. doi:10.1136/oem.2004.014795
Meier, R., Cascio, W. E., Ghio, A. J., Wild, P., Danuser, B., & Riediker, M. (2014). Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers. Environ Health Perspect, 122(7), 726-732. doi:10.1289/ehp.1307100
Monse, C., Hagemeyer, O., Raulf, M., Jettkant, B., van Kampen, V., Kendzia, B., . . . Merget, R. (2018). Concentration-dependent systemic response after inhalation of nano-sized zinc oxide particles in human volunteers. Part Fibre Toxicol, 15(1), 8. doi:10.1186/s12989-018-0246-4
Nelson, D. L., Nelson, D. L., Lehninger, A. L., & Cox, M. M. (2017). Lehninger Principles of biochemistry (Seventh edition ed.). Macmillan Higher Education: Basingstoke.
Poulsen, S. S., Knudsen, K. B., Jackson, P., Weydahl, I. E., Saber, A. T., Wallin, H., & Vogel, U. (2017). Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice. PLoS One, 12(4), e0174167. doi:10.1371/journal.pone.0174167
Sikkeland, L. I. B., Borander, A. K., Voie, O. A., Aass, H. C. D., Ovstebo, R., Aukrust, P., . . . Ueland, T. (2018). Systemic and Airway Inflammation after Exposure to Fumes from Military Small Arms. Am J Respir Crit Care Med, 197(10), 1349-1353. doi:10.1164/rccm.201709-1857LE
Walker, E. S., Fedak, K. M., Good, N., Balmes, J., Brook, R. D., Clark, M. L., . . . Peel, J. L. (2022). 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(3), 565-578. doi:10.1080/09603123.2020.1785402
Wyatt, L. H., Devlin, R. B., Rappold, A. G., Case, M. W., & Diaz-Sanchez, D. (2020). Low levels of fine particulate matter increase vascular damage and reduce pulmonary function in young healthy adults. Part Fibre Toxicol, 17(1), 58. doi:10.1186/s12989-020-00389-5