Complement activation in diabetic ketoacidosis brains

Hoffman, William H.; Cudrici, Cornelia; Zafranskaia, Ekaterina; Rus, Horea

doi:10.1016/j.yexmp.2005.12.007

Cited by 35 publications

(34 citation statements)

References 48 publications

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“…4C). As previously reported, CD59 expression was absent on the neuron, blood vessels and OLGs in the DKA brains (Hoffman et al, 2006). In normal brains, CD59 expression was found on neurons and blood vessels (as previously described (Singhrao et al, 1999)) and on the CP epithelial cells and ependymal cells (data not shown).…”

Section: Inos Icam-1 and Hsp70 Expression In Cp-inos (supporting

confidence: 87%

“…4 A, B). In the same brains as previously reported, up to 60-80% of neurons and OLGs displayed C5b-9 deposits (Hoffman et al, 2006). C5b-9 deposits were absent in the normal brains examined (data not shown).…”

Section: Inos Icam-1 and Hsp70 Expression In Cp-inos (supporting

confidence: 84%

“…C5b-9 can have a cytolytic effect and, at lower concentrations, can also activate pathways, which restrict injury and facilitate recovery of cells . C5b-9 has recently been reported to be deposited on neurons, oligodendrocytes (OLGs) and blood vessels in the fatal DKA (Hoffman et al, 2006). This finding supports the interaction between the immune and the central nervous systems and the hypothesis that in addition to the SIR, there is also a local neuroinflammatory component in the fatal cerebral complication of BE in DKA.…”

Section: Introductionsupporting

confidence: 60%

“…We selected known markers of an inflammatory response: IL-1β, TNF-α and C5b-9, iNOS, ICAM-1, IL-10 and hsp70. Immunohistochemistry was used the distribution of these markers of inflammatory response in the brains of two previously reported adolescent females with T1DM who died of BE during the treatment of severe DKA (Hoffman et al, 2006). Our data show the presence of IL-1β, TNF-α, iNOS, ICAM-1 and C5b-9 in CP indicating the involvement neuroinflammatory response in the fatal brain edema of DKA.…”

Section: Introductionmentioning

confidence: 52%

“…The methodology for C5b-9 has previously been described in detail (Hoffman et al, 2006). After xylene deparaffinisation and epitope retrieval using a Target Retrieval Solution (DAKO Carpanteria, CA), sections were treated with 3% H 2 O 2 to remove endogenous peroxidase.…”

Section: Tissue Analysismentioning

confidence: 99%

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Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

Hoffman

Casanova

Cudrici

et al. 2007

Experimental and Molecular Pathology

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A systemic inflammatory response (SIR) occurs prior to and during the treatment of severe diabetic ketoacidosis (DKA). IL-1β, TNF-α and C5b-9 are components of SIR and have been speculated to be involved in the clinical brain edema (BE) of DKA. We studied IL-1β, TNF-α, C5b-9, inducible nitric oxide (iNOS), ICAM-1, IL-10 and Hsp70 expression in the brains of two patients who died as the result of clinical BE during the treatment of DKA. IL-1β was strongly expressed in the choroid plexus epithelium (CPE) and ependyma, and to a lesser extent in the hippocampus, caudate, white matter radiation of the pons, molecular layer of the cerebellum and neurons of the cortical gray matter. TNF-α was expressed to a lesser extent than IL-1 β, and only in the CP. C5b-9, previously shown to be deposited on neurons and oligodendrocytes, was found on CPE and ependymal cells. iNOS and ICAM-1 had increased expression in the CPE and ependyma. Hsp70 and IL-10 were also expressed in the CPE of the case with the shorter duration of treatment. Our data demonstrates the presence of a multifaceted neuroinflammatory cytotoxic insult of the CPE, which may play a role in the pathophysiology of the fatal brain edema of DKA.

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Section: Inos Icam-1 and Hsp70 Expression In Cp-inos (supporting

confidence: 87%

Section: Inos Icam-1 and Hsp70 Expression In Cp-inos (supporting

confidence: 84%

Section: Introductionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 52%

Section: Tissue Analysismentioning

confidence: 99%

See 3 more Smart Citations

Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

Hoffman

Casanova

Cudrici

et al. 2007

Experimental and Molecular Pathology

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Membrane attack by complement: the assembly and biology of terminal complement complexes

et al. 2011

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Complement system activation plays an important role in both innate and acquired immunity. Activation of complement and the subsequent formation of C5b-9 channels (the membrane attack complex) on cell membranes lead to cell death. However, when the number of channels assembled on the surface of nucleated cells is limited, sublytic C5b-9 can induce cell cycle progression by activating signal transduction pathways and transcription factors and inhibiting apoptosis. This induction by C5b-9 is dependent upon the activation of the phosphatidylinositol 3-kinase/Akt/FOXO1 and ERK1 pathways in a Gi protein-dependent manner. C5b-9 induces sequential activation of CDK4 and CDK2, enabling the G1/S-phase transition and cellular proliferation. In addition, it induces RGC-32, a novel gene that plays a role in cell cycle activation by interacting with Akt and the cyclin B1-CDC2 complex. C5b-9 also inhibits apoptosis by inducing the phosphorylation of Bad and blocking the activation of FLIP, caspase-8, and Bid cleavage. Thus, sublytic C5b-9 plays an important role in cell activation, proliferation, and differentiation, thereby contributing to the maintenance of cell and tissue homeostasis.

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The role of complement system in adipose tissue-related inflammation

et al. 2016

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As the common factor linking adipose tissue to the metabolic context of obesity, insulin resistance and atherosclerosis are associated with a low-grade chronic inflammatory status, to which the complement system is an important contributor. Adipose tissue synthesizes complement proteins and is a target of complement activation. C3a-desArg/acylation-stimulating protein stimulates lipogenesis and affects lipid metabolism. The C3a receptor and C5aR are involved in the development of adipocytes' insulin resistance through macrophage infiltration and the activation of adipose tissue. The terminal complement pathway has been found to be instrumental in promoting hyperglycemia-associated tissue damage, which is characteristic of the major vascular complications of diabetes mellitus and diabetic ketoacidosis. As a mediator of the effects of the terminal complement complex C5b-9, RGC-32 has an impact on energy expenditure as well as lipid and glucose metabolic homeostasis. All of this evidence, taken together, indicates an important role for complement activation in metabolic diseases.

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Complement activation in diabetic ketoacidosis brains

Cited by 35 publications

References 48 publications

Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis

Membrane attack by complement: the assembly and biology of terminal complement complexes

The role of complement system in adipose tissue-related inflammation

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