The relative importance of local and systemic complement production in ischaemia, transplantation and other pathologies

Li, Ke; Sacks, Steven H.; Zhou, Wuding

doi:10.1016/j.molimm.2007.06.006

Cited by 111Complement system in diseasesBiomarkers in Disease MechanismsCoagulation, Bradykinin, Polyphosphates, and Angioedema

The relative importance of local and systemic complement production in ischaemia, transplantation and other pathologies

Li, Ke, Sacks, Steven H., Zhou, Wuding·2007·Molecular Immunology

DOI 10.1016/j.molimm.2007.06.006

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Abstract

Besides a critical role in innate host defence, complement activation contributes to inflammatory and immunological responses in a number of pathological conditions. Many tissues outside the liver (the primary source of complement) synthesise a variety of complement proteins, either constitutively or response to noxious stimuli. The significance of this local synthesis of complement has become clearer as a result of functional studies. It revealed that local production not only contributes to the systemic pool of complement but also influences local tissue injury and provides a link with the antigen-specific immune response. Extravascular production of complement seems particularly important at locations with poor access to circulating components and at sites of tissue stress responses, notably portals of entry of invasive microbes, such as interstitial spaces and renal tubular epithelial surfaces. Understanding the relative importance of local and systemic complement production at such locations could help to explain the differential involvement of complement in organ-specific pathology and inform the design of complement-based therapy. Here, we will describe the lessons we have learned over the last decade about the local synthesis of complement and its association with inflammatory and immunological diseases, placing emphasis on the role of local synthesis of complement in organ transplantation.

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Most complement proteins are produced in the liver, while others (C1q, C7, Factor D, and properdin) are produced at extrahepatic sites by various cells, including monocytes, macrophages, and glial and endothelial cells.
“While most complement proteins are produced in the liver, others (such as C1q, C7, Factor D, and properdin) are produced at extrahepatic sites by various cells, including monocytes, macrophages, and glial and endothelial cells [7,204,205].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [204]
In experimental mouse models, the renal tubular epithelium is more susceptible to donor kidney-derived C3.
“in experimental mouse models, the renal tubular epithelium has been found to be more susceptible to donor kidney-derived C3”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [204]
In experimental mouse models, the fenestrated capillaries of the renal glomerulus are more prone to systemic C3 activation.
“while the fenestrated capillaries of the renal glomerulus are more prone to systemic C3 activation [204,207].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [204]

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Hetland, G., Johnson, E., Falk, R. J., & ESKELAND, T. (1986) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1986.tb02130.x · Cited by 58 · see citing works
CD46 (Membrane Cofactor Protein) Acts as a Human Epithelial Cell Receptor for Internalization of Opsonized Uropathogenic Escherichia coli
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Cellular localization of complement C3 and C4 transcripts in intestinal specimens from patients with Crohn’s disease
Laufer, J., Oren, R., Goldberg, I., Horwitz, A., Kopolovic, J., Chowers, Y., & PASSWELL, J. H. (2000) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2000.01168.x · Cited by 57 · see citing works
Interleukin-1α enhances the biosynthesis of complement C3 and factor B by human kidney proximal tubular epithelial cells in vitro
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Complement Activation Regulates the Capacity of Proximal Tubular Epithelial Cell to Stimulate Alloreactive T Cell Response
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Human monocyte-derived dendritic cells are a source of several complement proteins
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Human keratinocytes produce the complement inhibitor factor I: Synthesis is regulated by interferon-γ
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Deficiency of C4 from Donor or Recipient Mouse Fails to Prevent Renal Allograft Rejection
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Expression of complement C4 and C9 genes by human astrocytes
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Unrestricted C3 Activation Occurs in Crry-Deficient Kidneys and Rapidly Leads to Chronic Renal Failure
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Interferon‐γ regulation of C4 gene expression in cultured human glomerular epithelial cells
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Compartmental Localization of Complement Component Transcripts in the Normal Human Kidney
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Interferon-gamma regulation of C3 gene expression in human astroglioma cells
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Production and interferon-γ-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG
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Synthesis of C3, C5, C6, C7, C8, and C9 by Human Fibroblasts
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Biosynthesis of Complement C4 Messenger RNA in Normal Human Kidney
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Local secretion of complement C3 in the exocrine pancreas: Ductal epithelial cells as a possible biosynthetic site
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Membrane Complement Regulatory Proteins in Autoimmune and Inflammatory Tissue Injury
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Biosynthesis of the Third and Fifth Complement Components by Isolated Human Lung Cells
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Human keratinocytes produce the complement inhibitor factor H: Synthesis is regulated by interferon-γ
Timár, K. K., Pasch, M. C., van den Bosch, N. H. A., Jarva, H., Junnikkala, S., Meri, S., Bos, J. D., & Asghar, S. S. (2005) · Molecular Immunology · doi:10.1016/j.molimm.2005.02.009 · Cited by 39 · see citing works
Complement gene expression in neuroblastoma and astrocytoma cell lines of human origin
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Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid
Tang, S. C. W., Leung, J. C. K., Chan, L. Y. Y., Tsang, A. W. L., CHEN, C. X. R., Zhou, W., Lai, K. N., & Sacks, S. H. (2004) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2004.02407.x · Cited by 31 · see citing works
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Human Keratinocytes and A-431 Cells Synthesize and Secret Factor B, the Major Zymogen Protease of the Alternative Complement Pathway
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Reduced expression of C1q-mRNA in monocytes from patients with systemic lupus erythematosus
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Tissue synthesis of complement as an immune regulator
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Complement activation by oxidatively modified low‐density lipoproteins
Wieland, W., Dorweiler, Bonitz, Lieser, Walev, & Bhakdi (1999) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1999.00548.x · Cited by 27 · see citing works
Intraglomerular C3 synthesis in rats with passive Heymann nephritis.
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Influence of complement C3 amount on IgG responses in early life: immunization with C3b-conjugated antigen increases murine neonatal antibody responses
Pihlgren, M., Fulurija, A., Villiers, M., Tougne, C., Lambert, P., VILLIERS, C. L., & Siegrist, C. (2004) · Vaccine · doi:10.1016/j.vaccine.2004.06.010 · Cited by 25 · see citing works
Synthesis of the third component of complement (C3) by lectin-activated and HTLV-infected human T-cells
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mRNA Expression of Complement Components and Regulators in Rat Arterial Smooth Muscle Cells
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Accumulation of immune complexes in glomerular disease is independent of locally synthesized c3
Sheerin, N. S., Abe, K., Risley, P., & Sacks, S. H. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2004070515 · Cited by 22 · see citing works
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Evidence for increased synthesis of complement C4 in the renal epithelium of rats with passive Heymann nephritis.
Zhou, W., Andrews, P., Wang, Y., Wolff, J., Pratt, J., HARTLEY, B., Verroust, P. J., & Sacks, S. H. (1997) · Journal of the American Society of Nephrology · doi:10.1681/asn.v82214 · Cited by 20 · see citing works
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Differential Cytokine Regulation of Complement Proteins in Human Glomerular Epithelial Cells
Laufer, J., Oren, R., Farzam, N., Goldberg, I., & PASSWELL, J. H. (2008) · The Nephron journals/Nephron journals · doi:10.1159/000190192 · Cited by 19 · see citing works
Biosynthesis and secretion of MHC class III gene products (complement C4 and factor B) in the exocrine pancreas
Sumiyoshi, K., Andoh, A., Fujiyama, Y., Sakumoto, H., & Bamba, T. (1997) · Journal of Gastroenterology · doi:10.1007/bf02934495 · Cited by 18 · see citing works
Allograft rejection: effect of local synthesis of complement
Sacks, S. H., & Zhou, W. (2005) · Springer Seminars in Immunopathology · doi:10.1007/s00281-005-0005-0 · Cited by 18 · see citing works
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Production of the third and fourth component of complement (C3, C4) by smooth muscle cells
Ueda, Y., NAGASAWA, K., Tsukamoto, H., HORIUCHI, T., Nishizaka, H., Ikeda, K., & Niho, Y. (1996) · Immunology · doi:10.1046/j.1365-2567.1996.d01-725.x · Cited by 17 · see citing works
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Complement and Its Receptors: New Insights into Human Disease
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Single-cell reconstruction of follicular remodeling in the human adult ovary
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Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a–C3aR interaction
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The Role of the Complement System and the Activation Fragment C5a in the Central Nervous System
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Therapeutic Targeting of Classical and Lectin Pathways of Complement Protects from Ischemia-Reperfusion-Induced Renal Damage
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Expression of Complement Components Differs Between Kidney Allografts from Living and Deceased Donors
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Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation.
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Complement 5a Receptor Inhibition Improves Renal Allograft Survival
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Expression of complement components, receptors and regulators by human dendritic cells
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C1 Complex: An Adaptable Proteolytic Module for Complement and Non-Complement Functions
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Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors
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Complement-dependent NADPH oxidase enzyme activation in renal ischemia/reperfusion injury
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Infiltrating dendritic cells contribute to local synthesis of C1q in murine and human lupus nephritis
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Properdin and factor H production by human dendritic cells modulates their T‐cell stimulatory capacity and is regulated by IFN‐γ
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Innate Immunity and Resistance to Tolerogenesis in Allotransplantation
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Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
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Decay-accelerating factor limits hemorrhage-instigated tissue injury and improves resuscitation clinical parameters
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Modifiers of complement activation for prevention of antibody-mediated injury to allografts
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Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine
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Generation of a C3c specific monoclonal antibody and assessment of C3c as a putative inflammatory marker derived from complement factor C3
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Additional file 11 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655429
Additional file 5 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655408
Additional file 10 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655426
Additional file 15 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655441
Additional file 13 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655435
Additional file 4 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655405
Additional file 14 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655438
Additional file 12 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655432
Additional file 9 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655423
Additional file 7 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655417
Additional file 6 of Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Li, S., Schmid, K., de Vries, D. H., Korshevniuk, M., Losert, C., Oelen, R., van Blokland, I. V., Groot, H. E., Swertz, M. A., van der Harst, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22655414

Authors: Li, K., Sacks, S. H., & Zhou, W.
Affiliations: Guy's Hospital (GB)
Corresponding author: Zhou, Wuding
ORCID: Li, Ke
Sacks, Steven H.
Zhou, Wuding
Venue: Molecular Immunology
Publisher: Elsevier BV
Published: 2007-09
Volume: 44
Issue: 16
Pages: 3866-3874
ISSN: 0161-5890 (ISSN-L)
DOI: 10.1016/j.molimm.2007.06.006
OpenAlex: W2062492768
Cited by: 98
References: 120
Citations by year: 2026: 3 · 2024: 2 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 1 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 5 · 2012: 5
FWCI: 0.48
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular Immunology (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: Wellcome Trust
Research Councils UK
Medical Research Council
Topics: Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
Keywords: organ transplantation, ischemia, tissue damage, inflammation, complement activation, renal tubular epithelium, innate immunity, antigen-specific immune response
MeSH terms: Animals, Complement System Proteins, Complement Activation, Disease, Humans, Ischemia, Organ Specificity, Transplantation Immunology

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The relative importance of local and systemic complement production in ischaemia, transplantation and other pathologies

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