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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Proinflammatory blood monocytes: main effector and target cells in systemic and renal disease; background and
1Second Medical Department, Hospital Munich-Harlaching, Academic Educational Hospital, Ludwig-Maximilians-University, Munich, Germany. JScherberich@Nierenzentrum.de
Abstract:
Although peripheral blood monocytes are heterogeneous, they all express the CD14 molecule, a multifunctional receptor, and part of the toll-like membrane receptor complex. In healthy persons, a minor subset (8%) coexpresses CD14 and CD16, a low affinity Fc-gamma type III receptor. This subpopulation shows characteristics of tissue macrophages and expands greatly in acute and chronic infections, systemic inflammatory syndromes, hyperlipidedemia, AIDS and renal failure. CD14+/CD16+ monocytes (Mo) exhibit higher phagocytosis activity than CD14++/CD16-negative monocytes and synthesize high levels of interleukin-1, TNF-alpha and HLA-DR, -DP and -DQ antigens. Glucocorticoids (and interleukin-4), and successful therapy in patients with inflammatory and septic complications lead to a down-regulation in the expression of CD14 and deplete CD14+/CD16+-proinflammatory Mo. Recovery of low monocytic HLA-DR expression parallels clinical improvement. Serial analyses of Mo phenotypes may be useful tools for monitoring patients receiving immunosuppressive and anti-inflammatory therapy respectively.
Insights
Peripheral blood monocytes, including CD14+/CD16+ subsets, play a key role in inflammatory conditions. Their CD14 and CD16 expression levels can be monitored to assess treatment efficacy in patients.
Area of Science:
- Immunology
- Cell Biology
Background:
- Peripheral blood monocytes are heterogeneous but share CD14 expression.
- A minor subset, CD14+/CD16+ monocytes, exhibits macrophage-like properties and expands during inflammation.
Purpose of the Study:
- To investigate the role and characteristics of CD14+/CD16+ monocytes.
- To explore the potential of monocyte phenotype analysis for monitoring therapeutic responses.
Main Methods:
- Flow cytometry analysis of monocyte surface markers (CD14, CD16, HLA-DR).
- Assessment of cytokine production (interleukin-1, TNF-alpha) and phagocytic activity.
- Monitoring changes in monocyte phenotypes in response to therapy.
Main Results:
- CD14+/CD16+ monocytes show enhanced phagocytosis and higher pro-inflammatory cytokine synthesis.
- Glucocorticoids and successful anti-inflammatory therapy down-regulate CD14 and deplete CD14+/CD16+ monocytes.
- Recovery of monocytic HLA-DR expression correlates with clinical improvement.
Conclusions:
- CD14+/CD16+ monocytes are key players in inflammatory and infectious diseases.
- Monitoring monocyte phenotypes, particularly CD14 and CD16 expression, can serve as a valuable tool for assessing patient recovery and therapeutic effectiveness in inflammatory conditions.
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