Moonlighting chromatin: when DNA escapes nuclear control

Abstract

Extracellular chromatin, for example in the form of neutrophil extracellular traps (NETs), is an important element that propels the pathological progression of a plethora of diseases. DNA drives the interferon system, serves as autoantigen, and forms the extracellular scaffold for proteins of the innate immune system. An insufficient clearance of extruded chromatin after the release of DNA from the nucleus into the extracellular milieu can perform a secret task of moonlighting in immune-inflammatory and occlusive disorders. Here, we discuss (I) the cellular events involved in the extracellular release of chromatin and NET formation, (II) the devastating consequence of a dysregulated NET formation, and (III) the imbalance between NET formation and clearance. We include the role of NET formation in the occlusion of vessels and ducts, in lung disease, in autoimmune diseases, in chronic oral disorders, in cancer, in the formation of adhesions, and in traumatic spinal cord injury. To develop effective therapies, it is of utmost importance to target pathways that cause decondensation of chromatin during exaggerated NET formation and aggregation. Alternatively, therapies that support the clearance of extracellular chromatin are conceivable.

Salivary Biochemistry Associated with Helicobacter Pylori Positivity in Patients with Chronic Gastritis

“…The information will fully illustrate how saliva and ocular homeostasis are involved in the immune-inflammatory pathways and the changes to gastric mucosa. (15) It has been established that H. pylori may have a role in the aetiology of a number of oral disorders, including periodontal disease, recurring aphthous stomatitis, burning mouth syndrome, halitosis and squamous cell carcinoma. The development of bacterium in saliva and dental plaque seems to serve as reservoir for infection of stomach and the reinfection.…”

“…The concentration of salivary protein is not change and self-reliant from the salivary flow rate, about (30-40 %) of salivary proteins are performed by salivary glands, while other proteins are arisenfrom mucosal, immune cells, blood and /or from microorganisms (14) . The salivary protein has antimicrobial defense, part of defense are implicated mainly in activation of immunity like salivary immunoglobulin's (15) , while others protein are responsible for non-immune elimination of microbes like salivary amylase by inhibitory effect on microorganism growth (16) . It is believed that the infection with gastric H. pylori mainly occurs at the same time when the dental plaque pathogen was founded "when the pathogenic strains are shared in mucosa of human stomach and dental plaque" (17).…”

Unveiling the nexus: Decoding interactions between regulated cell death and systemic lupus erythematosus pathogenesis for innovative therapeutic avenues

“…Some drugs (e.g., procainamide) induce lupus‐like symptoms by promoting NET formation 47 . Kinase‐mediated disassembly and envelope rupture of the nuclear lamina amplify entry of decondensation enzymes, facilitating nuclear chromatin decondensation and extracellular NET release 48 . Protein kinase C (PKC)α and cyclin‐dependent kinases (CDK)4/6 affect the nuclear alterations and mechanisms that precipitate nuclear envelope rupture, a pivotal event in NETosis.…”

Antibodies to Neutrophil Extracellular Traps: Novel Markers for the Antiphospholipid Syndrome

“…In this issue of Arthritis & Rheumatology , a provocative serologic analysis by Zuo et al provides a novel perspective on autoantibody expression in patients with antiphospholipid antibodies (aPL) (1). As the data from a large patient cohort indicate, patients whose serum is persistently positive for APL, including those with the antiphospholipid syndrome (APS), produce IgM and IgG antibodies to neutrophil extracellular traps (NETs), a large DNA‐rich structure released by activated neutrophils (2,3). Furthermore, these patients can display antibodies to DNA and nucleosomes, both specific markers of systemic lupus erythematosus (SLE).…”

“…As defined by microscopy and biochemistry, NETs are large assemblages or conglomerations of DNA and cytoplasmic proteins from the neutrophil; other immune cells can also produce these structures. Variously described as meshes, webs, or tangles, NETs present a formidable defense against infection, with molecular adhesiveness bolstering their ability to ensnare and kill bacteria and fungi (2,3).…”