| Title |
Hemoadsorption corrects hyperresistinemia and restores anti-bacterial neutrophil function
|
|---|---|
| Published in |
Intensive Care Medicine Experimental, August 2017
|
| DOI | 10.1186/s40635-017-0150-5 |
| Pubmed ID | |
| Authors |
Anthony Bonavia, Lauren Miller, John A. Kellum, Kai Singbartl |
| Abstract |
Mounting evidence suggests that sepsis-induced morbidity and mortality are due to both immune activation and immunosuppression. Resistin is an inflammatory cytokine and uremic toxin. Septic hyperresistinemia (plasma resistin >20 ng/ml) has been associated with greater disease severity and worse outcomes, and it is further exacerbated by concomitant acute kidney injury (AKI). Septic hyperresistinemia disturbs actin polymerization in neutrophils leading to impaired neutrophil migration, a crucial first-line mechanism in host defense to bacterial infection. Our experimental objective was to study the effects of hyperresistinemia on other F-actin-dependent neutrophil defense mechanisms, in particular intracellular bacterial clearance and generation of reactive oxygen species (ROS). We also sought to examine the effects of hemoadsorption on hyperresistinemia and neutrophil dysfunction. Thirteen patients with septic shock and six control patients were analyzed for serum resistin levels and their effects on neutrophil migration. In vitro, following incubation with resistin-spiked serum samples, Pseudomonas aeruginosa clearance and ROS generation in neutrophils were measured. Phosphorylation of 3-phosphoinositide-dependent protein kinase-1 (PDPK1) was assessed using flow cytometry. In vitro hemoadsorption with both Amberchrome™ columns (AC) and CytoSorb® cartridges (CC) were used to test correction of hyperresistinemia. We further tested AC for their effect on cell migration and ROS generation and CC for their effect on bacterial clearance. Patients with septic shock had higher serum resistin levels than control ICU patients and showed a strong, negative correlation between hyperresistinemia and neutrophil transwell migration (ρ= - 0.915, p < 0.001). In vitro, neutrophils exposed to hyperresistinemia exhibited twofold lower intracellular bacterial clearance rates compared to controls. Resistin impaired intracellular signaling and ROS production in a dose-dependent manner. Hemoadsorption with AC reduced serum concentrations of resistin and restored neutrophil migration and generation of ROS to normal levels. Hemoadsorption with CC also corrected hyperresistinemia and reconstituted normal intracellular bacterial clearance. Septic hyperresistinemia strongly correlates with inhibition of neutrophil migration in vitro. Hyperresistinemia itself reversibly impairs neutrophil intracellular bacterial clearance and ROS generation. Hemoadsorption therapy with a clinically approved device corrects hyperresistinemia and neutrophil dysfunction. It may therefore provide a therapeutic option to improve neutrophil function during septic hyperresistinemia and ultimately alleviate immunosuppression in this disease state. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 25% |
| Belgium | 1 | 25% |
| United States | 1 | 25% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 22 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 27% |
| Student > Doctoral Student | 3 | 14% |
| Researcher | 3 | 14% |
| Professor | 2 | 9% |
| Lecturer | 1 | 5% |
| Other | 4 | 18% |
| Unknown | 3 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 41% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
| Biochemistry, Genetics and Molecular Biology | 1 | 5% |
| Immunology and Microbiology | 1 | 5% |
| Veterinary Science and Veterinary Medicine | 1 | 5% |
| Other | 4 | 18% |
| Unknown | 5 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 December 2017.
All research outputs
#12,856,775
of 22,996,001 outputs
Outputs from Intensive Care Medicine Experimental
#199
of 449 outputs
Outputs of similar age
#146,295
of 317,469 outputs
Outputs of similar age from Intensive Care Medicine Experimental
#9
of 12 outputs
Altmetric has tracked 22,996,001 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 449 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has gotten more attention than average, scoring higher than 54% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 317,469 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.