| 1. |
- Björnsdottir, Halla, et al.
(författare)
-
Neutrophil NET formation is regulated from the inside by myeloperoxidase-processed reactive oxygen species.
- 2015
-
Ingår i: Free radical biology & medicine. - : Elsevier BV. - 1873-4596 .- 0891-5849. ; 89, s. 1024-1035
-
Tidskriftsartikel (refereegranskat)abstract
- Neutrophil extracellular traps (NETs) are mesh-like DNA fibers clad with intracellular proteins that are cast out from neutrophils in response to certain stimuli. The process is thought to depend on reactive oxygen species (ROS) generated by the phagocyte NADPH-oxidase and the ROS-modulating granule enzyme myeloperoxidase (MPO), but when, how, and where these factors contribute is so far uncertain. The neutrophil NADPH-oxidase can be activated at different cellular sites and ROS may be produced and processed by MPO within intracellular granules, even in situations where a phagosome is not formed, e.g., upon stimulation with phorbol myristate acetate (PMA).
|
|
| 2. |
- Sundqvist, Martina, et al.
(författare)
-
Increased intracellular oxygen radical production in neutrophils during febrile episodes of PFAPA syndrome.
- 2013
-
Ingår i: Arthritis and rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 65:11
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome is an autoinflammatory disease of unknown etiology that primarily affects preschool children. PFAPA is characterized by recurrent attacks of fever and inflammatory symptoms consistent with the disease acronym. Since autoinflammatory diseases by definition are mediated by cells of the innate immune system, we aimed at evaluating functional features of neutrophils, the most abundant innate immune cell in circulation, in PFAPA syndrome. Methods: Blood neutrophils, obtained from PFAPA patients during both febrile and asymptomatic afebrile phases of disease, as well as from healthy children (afebrile controls) and children with fever and abdominal pain (febrile controls) were analysed for three key neutrophil characteristics: (i) apoptosis (measured by Annexin V/7AAD staining), (ii) production of reactive oxygen species (ROS; by luminol/isoluminol-amplified chemiluminescence), and (iii) priming status (as responsiveness to galectin-3 and upregulation of CD11b). Results: Compared to neutrophils from both PFAPA patients in an afebrile interval and from febrile controls, neutrophils obtained during a PFAPA flare produced elevated levels of intracellular NADPH-oxidase-derived ROS, had significantly diminished rates of spontaneous apoptosis, and displayed signatures of priming. In contrast, neutrophils from afebrile PFAPA patients had a significantly elevated rate of spontaneous apoptosis compared to neutrophils from afebrile controls. Conclusions: We demonstrate that three key aspects of neutrophil innate immune function, namely apoptosis, priming, and generation of an intracellular oxidative burst are altered, most prominently during febrile attacks in PFAPA syndrome. © 2013 American College of Rheumatology.
|
|
| 3. |
- Sundqvist, Martina, et al.
(författare)
-
Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition
- 2023
-
Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient’s symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1β, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed.
|
|
| 4. |
|
|
