Crosstalk between the renin–angiotensin, complement and kallikrein–kinin systems in inflammation
Open accessAbstract
During severe inflammatory and infectious diseases, various mediators modulate the equilibrium of vascular tone, inflammation, coagulation and thrombosis. This Review describes the interactive roles of the renin-angiotensin system, the complement system, and the closely linked kallikrein-kinin and contact systems in cell biological functions such as vascular tone and leakage, inflammation, chemotaxis, thrombosis and cell proliferation. Specific attention is given to the role of these systems in systemic inflammation in the vasculature and tissues during hereditary angioedema, cardiovascular and renal glomerular disease, vasculitides and COVID-19. Moreover, we discuss the therapeutic implications of these complex interactions, given that modulation of one system may affect the other systems, with beneficial or deleterious consequences.
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Activation of plasma and tissue kallikreins by factor XII results in synthesis of bradykinins.
“The activation of plasma and tissue kallikreins by factor X II, also known as an important initiator of blood coagulation and aminopeptidases, respectively, results in the synthesis of bradykinins [107].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [107]
The KKS/contact system section says FXIIa activates plasma kallikrein, which releases bradykinin. It says tissue kallikrein is activated by an unknown protease, not factor XII, and releases kallidin rather than bradykinin directly. (LLM, conf=0.90)
Experimental — accuracy not yet measuredDuring severe inflammatory physiology and diseases, the RAS is an important part of inflammatory response regulation.
“At the same time, during severe inflammatory physiology and diseases, the RAS is an important part of inflammatory response regulation [62, 63].”
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Defining blood-induced microglia functions in neurodegeneration through multiomic profiling
Mendiola, A. S., Yan, Z., Dixit, K., Johnson, J. R., Bouhaddou, M., Meyer-Franke, A., Shin, M.-G., Yong, Y., Agrawal, A., MacDonald, E., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01522-0 · Cited by 124 · see citing works
Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis
Subhan, M. A., Parveen, F., Filipczak, N., Yalamarty, S. S. K., & Torchilin, V. P. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13030389 · Cited by 98 · see citing works
“The activation of plasma and tissue kallikreins by factor X II, also known as an important initiator of blood coagulation and aminopeptidases, respectively, results in the synthesis of bradykinins [107].”
BackgroundWei, L., Bo, L., Luo, C., Yin, N., Jiang, W., Qian, F., Zhou, A., Lu, X., Guo, H., & Mao, C. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03997-6 · Cited by 11 · see citing works
“At the same time, during severe inflammatory physiology and diseases, the RAS is an important part of inflammatory response regulation [62, 63].”
Background
- Authors
- Bekassy, Z., Lopatko Fagerström, I., Bader, M., & Karpman, D.
- Affiliations
- Lund University (SE)
- Corresponding author
- Karpman, Diana
- Venue
- Nature reviews. Immunology
- Published
- 2021-11-10
- Volume
- 22
- Issue
- 7
- Pages
- 411-428
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC8579187
- OpenAlex
- W3211940634
- Cited by
- 167
- References
- 290
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 46 · 2023: 42 · 2022: 20
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB1365)
- Crafoordska Stiftelsen
- Knut och Alice Wallenbergs Stiftelse (Wallenberg Clinical Scholar 2015.0320, 2015.0320)
- Vetenskapsrådet (2017-01920)
- Topics
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- renin-angiotensin system, complement system, kallikrein-kinin system, contact system, inflammation, hereditary angioedema, vasculitis, glomerular disease, COVID-19 pandemic, vascular tone, vascular leakage, thrombosis, chemotaxis, cell proliferation, cardiovascular disease, kidney disease, therapeutic target
- MeSH terms
- COVID-19, Complement System Proteins, Humans, Inflammation, Renin-Angiotensin System, Thrombosis, Kallikrein-Kinin System
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