Cell damage and autoimmunity: A critical appraisal

Mackay, Ian R.; Leskovsek, Natasha; Rose, Noel R.

doi:10.1016/j.jaut.2007.11.009

Cited by 142 publications

(109 citation statements)

References 87 publications

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“…It has been suggested that the principal event leading to inflammatory diseases is cell damage as a result of apoptosis or necrosis (36,52,56). Increased permeability of the epithelial barrier and increased apoptotic rates of epithelial cells have been implicated to be major factors in the pathogenesis of intestinal inflammation (25,64).…”

Section: Discussionmentioning

confidence: 99%

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

Kum

2011

Infect Immun

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The Salmonella effector protein SopB has previously been shown to induce activation of Akt and protect epithelial cells from apoptosis in vitro. To characterize the role of Akt2 in host defense against Salmonella enterica serovar Typhimurium infection, wild-type (WT) mice and mice lacking Akt2 (Akt2 knockout [KO] mice) were infected using a Salmonella acute gastroenteritis model. Infected Akt2 KO mice showed a more pronounced morbidity and mortality associated with higher bacterial loads in the intestines and elevated levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-␣), gamma interferon (IFN-␥), and MCP-1, in the colons at 1 day postinfection compared to those shown in WT mice. Histopathological assessment and immunohistochemical analysis of cecal sections at 1 day postinfection revealed more severe inflammation and higher levels of neutrophil infiltration in the ceca of Akt2 KO mice. Flow cytometry analysis further confirmed an increase in the recruitment of Gr-1 ؉ CD11b ؉ neutrophils and F4/80 ؉ CD11b ؉ macrophages in the intestines of infected Akt2 KO mice. Additionally, enhanced levels of annexin V ؉ and terminal transferase dUTP nick end labeling-positive (TUNEL ؉ ) apoptotic cells in the intestines of infected Akt2 KO mice were also observed, indicating that Akt2 plays an essential role in protection against apoptosis. Finally, the differences in bacterial loads and cecal inflammation in WT and Akt2 KO mice infected with WT Salmonella were abolished when these mice were infected with the sopB deletion mutant, indicating that SopB may play a role in protecting the mice from Salmonella infection through the activation of Akt2. These data demonstrate a definitive phenotypic abnormality in the innate response in mice lacking Akt2, underscoring the important protective role of Akt2 in Salmonella infection.

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Section: Discussionmentioning

confidence: 99%

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

Kum

2011

Infect Immun

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“…Several factors have been implicated in the pathogenesis of autoimmune disorders, including altered apoptosis [245]. Although autoimmunity may not follow impaired clearance of apoptosing cells [70,246,247], many studies show that such an impairment may result in immunogenicity and autoimmune disorders.…”

Section: Secondary Necrosis In Autoimmune Diseasesmentioning

confidence: 99%

Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications

2008

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In metazoans apoptosis is a major physiological process of cell elimination during development and in tissue homeostasis and can be involved in pathological situations. In vitro, apoptosis proceeds through an execution phase during which cell dismantling is initiated, with or without fragmentation into apoptotic bodies, but with maintenance of a near-to-intact cytoplasmic membrane, followed by a transition to a necrotic cell elimination traditionally called "secondary necrosis". Secondary necrosis involves activation of self-hydrolytic enzymes, and swelling of the cell or of the apoptotic bodies, generalized and irreparable damage to the cytoplasmic membrane, and culminates with cell disruption. In vivo, under normal conditions, the elimination of apoptosing cells or apoptotic bodies is by removal through engulfment by scavengers prompted by the exposure of engulfment signals during the execution phase of apoptosis; if this removal fails progression to secondary necrosis ensues as in the in vitro situation. In vivo secondary necrosis occurs when massive apoptosis overwhelms the available scavenging capacity, or when the scavenger mechanism is directly impaired, and may result in leakage of the cell contents with induction of tissue injury and inflammatory and autoimmune responses. Several disorders where secondary necrosis has been implicated as a pathogenic mechanism will be reviewed.

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“…The direct causes of autoimmune diseases remain unclear, but it is known that in addition to genetic factors, environmental triggers such as viruses, bacteria and other pathogens can participate in the development of autoimmune diseases [57]. Autoimmunity is also closely associated with inflammation, although the role of inflammation in the development of autoimmunity is still a subject of investigation [59]. In many autoimmune and infectious diseases (rheumatoid arthritis (RA), active Crohn's disease, tuberculosis, Lyme disease, sarcoidosis, etc.…”

Section: Sialylation α-13-galactosylation and Microorganismsmentioning

confidence: 99%

“Lost sugars” — reality of their biological and medical applications

Talafová¹,

Nahálka²

2012

Open Life Sciences

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The glycan chains attached to cell surfaces or to single proteins are highly dynamic structures with various functions. The glycan chains of mammals and of some microorganisms often terminate in sialic acids or α-1,3-galactose. Although these two sugars are completely distinct, there are several similarities in their biological and medical importance. First, one type of sialic acid, N-glycolylneuraminic acid, and the galactose bound by an α-1,3-linkage to LacNAc, that forms an α-gal epitope, were both eliminated in human evolution, resulting in the production of antibodies to these sugars. Both of these evolutionary events have consequences connected with the consumption of foods of mammalian origin, causing medical complications of varying severity. In terms of ageing, sialic acids prevent the clearance of glycoproteins and circulating blood cells, whereas cryptic α-gal epitopes on senescent red blood cells contribute to their removal from circulation. The efficiency of therapeutic proteins can be increased by sialylation. Another common feature is the connection with microorganisms since sialic acids and α-gal epitopes serve as receptors on host cells and can also be expressed on the surfaces of some microorganisms. Whereas, the sialylation of IgG antibodies may help to treat inflammation, the expression of the α-gal epitope on microbial antigens increases the immunogenicity of the corresponding vaccines. Finally, sialic acids and the α-gal epitope have applications in cancer immunotherapy. N-glycolylneuraminic acid is a powerful target for cancer immunotherapy, and the α-gal epitope increases the efficiency of cancer vaccines. The final section of this article contains a brief overview of the methods for oligosaccharide chain synthesis and the characteristics of sialyltransferases and α-1,3-galactosyltransferase.

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Cell damage and autoimmunity: A critical appraisal

Cited by 142 publications

References 87 publications

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications

“Lost sugars” — reality of their biological and medical applications

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