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Frustrated phagoytosis leads to Release, Cytokine
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Phagocytosis allow the clearance of foreign matter. Incomplete phagocytosis, or frustrated phagocytosis, leads to the persistence of foreign matter. Therefore, in order to clear these substances, phagocytes secretes signals including cytokines for the recruitment of other phagocytes.
Evidence Supporting this KER
Uncertainties and Inconsistencies
In very few studies it was analysed the release of cytokines in the same samples as the frustrated phagocytosis.
A study of Zeidler-Erdely et al 2006 showed that human alveolar macrophages are able to engulf fibres with a length of 20 µm and explained this difference with rat alveolar macrophages are smaller than human cells . However, these data are not in accordance with those obtained by Sweeney et al 2015 were they used primary human alveolar macrophages and by Murphy et al 2012 were they used monocytic cells THP-1 differentiated in macrophages [2, 3].
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
1. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. 2011;11 11:723-37; doi: 10.1038/nri3073.
2. Murphy FA, Schinwald A, Poland CA, Donaldson K. The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells. Particle and fibre toxicology. 2012;9:8; doi: 10.1186/1743-8977-9-8.
3. Sweeney S, Grandolfo D, Ruenraroengsak P, Tetley TD. Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes. International journal of nanomedicine. 2015;10:3115-29; doi: 10.2147/IJN.S77867.
4. Padmore T, Stark C, Turkevich LA, Champion JA. Quantitative analysis of the role of fiber length on phagocytosis and inflammatory response by alveolar macrophages. Biochimica et biophysica acta. 2017;1861 2:58-67; doi: 10.1016/j.bbagen.2016.09.031.
5. Ye J, Shi X, Jones W, Rojanasakul Y, Cheng N, Schwegler-Berry D, et al. Critical role of glass fiber length in TNF-alpha production and transcription factor activation in macrophages. 1999;276 3:L426-34; doi: 10.1152/ajplung.1999.276.3.L426.
6. Zeidler-Erdely PC, Calhoun WJ, Ameredes BT, Clark MP, Deye GJ, Baron P, et al. In vitro cytotoxicity of Manville Code 100 glass fibers: effect of fiber length on human alveolar macrophages. 2006;3:5; doi: 10.1186/1743-8977-3-5.