Background Lymphocytes secrete IL-17A and IL-17F, which enhance innate immune responses. IL-17 expression has not been studied in COPD small airways. The aim of this study was to quantify IL-17A and ...IL-17F expression in the peripheral lung tissue of patients with COPD compared with control subjects and to identify inflammatory cells that express IL-17. Methods IL-17 expression was assessed using immunohistochemistry in peripheral lung tissue (18 patients with COPD and 10 smokers and 10 nonsmokers with normal lung function) and induced sputum (12 patients with COPD and six nonsmokers). Alveolar macrophages from eight patients with COPD, eight smokers, and seven nonsmokers were used for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Results The number of inflammatory cells expressing IL-17A in the small airway subepithelium was higher in patients with COPD than in smokers ( P = .01) and nonsmokers ( P = .02). IL-17A expression was higher than IL-17F in this region. IL-17A was expressed by lymphocytes, neutrophils, and macrophages (confirmed by RT-PCR). The expression of IL-17F was greater than IL-17A in epithelial cells and lymphoid follicles, although there were no differences among subject groups. Conclusions Our findings indicate different roles for IL-17A and IL-17F in the pathogenesis of COPD. IL-17A plays a role in small airway subepithelial inflammation, whereas IL-17F appears to play a more prominent role within lymphoid follicles.
T regulatory cells (Tregs) may play a role in the suppression of effector lymphocyte activity in asthma. We hypothesized that Treg numbers would be increased in patients with more severe asthma. We ...also investigated the regulatory function of CD4 cells by expression of cytotoxic T-lymphocyte antigen 4 (CTLA4), and the number of these cells that are intraepithelial lymphocytes expressing CD103.
The primary aim was to investigate Treg numbers in the BAL of patients with moderate to severe asthma compared with mild asthma and healthy controls. The secondary aim was to investigate BAL CD4(+)CTLA4 and CD4(+)CD103 expression in these groups.
Airway lymphocytes obtained by bronchoscopy from healthy control subjects (six) and patients with mild (15) and moderate to severe (13) asthma were characterized by multiparameter flow cytometric analysis using three methods to determine the numbers of CD4(+) Treg cells: CD4(+)CD25(bright), CD4(+)CD25(+)CD127(-), and CD4(+)FoxP3(+).
The %CD4(+)FoxP3(+) Tregs were increased in the BAL of patients with moderate to severe asthma (median 4.8%) compared with both mild asthma patients (median 2.5%, P = .03) and healthy subjects (median 0.95, P = .003). Similar findings were observed for CD4(+)CD25(+)CD127(-) Treg numbers, but not CD4CD25(bright). CD4(+) CTLA4 and CD103 expressions were raised in moderate to severe asthma patients compared with those with mild asthma and healthy controls.
The number of cells displaying regulatory capacity, either through FoxP3 expression or CTLA4 expression, is increased in moderate to severe asthma. CD4(+)CD103(+) intraepithelial lymphocytes can be retained at tissue sites of inflammation; our findings indicate a role for these cells in asthma pathophysiology.
More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use ...of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m
of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD).
Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval CI, 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups.
Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).
The numbers of airway CD8 and B lymphocytes are increased in COPD patients, suggesting an autoimmune process. CD4-regulatory T cells control autoimmunity but have not been studied in patients with ...COPD.
To compare T-regulatory cell numbers in the BAL from COPD patients, smokers with normal lung function, and healthy nonsmokers (HNS).
BAL and peripheral blood mononuclear cell (PBMC) samples were obtained from 26 COPD patients, 19 smokers, and 8 HNS. Flow cytometry was performed for regulatory phenotypic markers.
COPD patients had increased BAL CD8 numbers compared to smokers and HNS. CD4 numbers were similar between groups. There was increased BAL CD4CD25(bright) expression in smokers (median 28.8%) and COPD patients (median 23.1%) compared to HNS (median 0%). Increased FoxP3 expression was confirmed in BAL CD4CD25(bright) cells. BAL CD4CD25 cells expressed less CD27 compared to PBMCs, suggesting weaker functional regulatory ability.
Chronic cigarette smoke exposure up-regulates airway CD4 regulatory cell numbers. Their function may be to control pulmonary inflammation.
Most monitoring studies of marine anthropogenic debris have focused on sandy beaches, so little is known about litter on rocky shorelines. We surveyed litter trapped on a rocky intertidal shore in ...False Bay, South Africa, between May 2015 and March 2018. An exceptional upwelling of seabed litter occurred in November 2017 (70 items∙m−1). Excluding this event, monthly clean-ups at spring low tide collected 2 (1.3–3.1) items∙m−1∙month−1 and 31 (19.4–49.4) g∙m−1∙month−1 of which 74% was plastic (31% by mass). Litter loads peaked in autumn when seasonal rains washed litter into False Bay, suggesting that most litter comes from local land-based sources. Litter composition differed from that on a nearby sandy beach, with more glass and other dense items on the rocky shore, but 60% of plastic items floated in water. Sand inundation and biotic interactions helped to trap buoyant plastics in the intertidal zone.
•One of few studies to monitor litter trapped on a rocky intertidal shore•Plastics made up 74% of litter by count but only 31% by mass.•Most plastic was disposable flexible packaging (bags and food packaging).•Litter loads 1–2 orders of magnitude higher than average during an upwelling event.•Rocky shore trapped more bags/packets, but less rigid plastics, than nearby sandy beach.
There are increased numbers of activated lymphocytes in the lungs of chronic obstructive pulmonary disease (COPD) patients. The clinical benefits of corticosteroids in COPD patients are limited. Our ...hypothesis is that lymphocytes play a role in this corticosteroid insensitivity.
To investigate the effects of the corticosteroid dexamethasone on lung lymphocyte cytokine production from patients with COPD compared to controls.
Cultured airway lymphocytes obtained by bronchoscopy from healthy non-smokers (HNS), smokers (S) and COPD patients were stimulated with phytohaemagglutinin (PHA) & phorbol myristate acetate (PMA), +/- dexamethasone. Supernatants were assayed for interleukin (IL)-2 and interferon (IFN)γ. Immunofluoresence was used to analyse changes in CD8 glucocorticoid receptor (GRα and GRβ) expression.
The inhibition of PHA/PMA stimulated IFNγ production by dexamethasone was reduced in COPD patients compared to HNS (p < 0.05 at concentrations from 0.1-1 μM). There was also a significant reduction (p < 0.05) in the mean inhibitory effect at 1 μM in COPD patients (54.1%) compared to smokers (72.1%), and in smokers compared to HNS (85.5%). There was a numerically reduced effect of dexamethasone on IL-2 production that did not reach statistical significance. There was no difference in GRα and GRβ expression in follicular CD8 cells between COPD patients (50.9% and 30.4% respectively) and smokers (52.9% and 29.7% respectively).
IFNγ production from COPD airway lymphocytes is corticosteroid insensitive. This phenomenon may be important in the poor clinical response often observed with corticosteroids.
Invasive rodents threaten native species in numerous ecosystems, especially oceanic islands. The House Mouse
Mus musculus
is the only introduced mammal species on sub-Antarctic Gough and Marion ...Islands. Ample evidence exists of mice preying upon seabird chicks on these two islands, but there have been only a few reports of attacks on adult seabirds, none of which has been fatal. We report the first deaths of adult great albatrosses due to mouse attacks. On Gough Island, three Tristan Albatrosses
Diomedea dabbenena
(Critically Endangered) brooding small chicks were observed with wounds typical of mouse attacks in March–April 2021; two likely abandoned their chick, causing breeding failure, and the third was found dead eight days after discovery with large blowfly larvae in the wound. On Marion Island, two wounded and eight dead adult Wandering Albatrosses
D. exulans
(Vulnerable) were found in April 2023. Inspection of the wounded individuals, as well as the injuries on the fresh carcasses strongly suggest that mouse predation was the cause of death. Gough Island is home to virtually all Tristan Albatrosses, and Marion Island is the single most important breeding site for Wandering Albatrosses, home to about a quarter of all breeding birds. The death of breeding adults of these long-lived species emphasizes the urgent need to eradicate introduced mice from these islands.
Understanding a lspecies' diet can be critical for effective conservation. While several traditional methods for assessing raptor diet exist, many pose inherit biases and often require extensive ...fieldwork that can limit sample sizes and the geographic scope of studies. This is especially true for species that nest at low densities (e.g., large eagles). Recently, several studies have demonstrated the value of web-sourced photographs in tackling ecological and evolutionary questions. Specialized software (e.g., MORPHIC) has been developed to systematically extract Google Images for this purpose. We used this approach to explore the diet of Martial Eagles (Polemaetus bellicosus). A shortage of prey is one of the proposed hypotheses for recent population declines across their range. Of the 4,872 photographs selected by MORPHIC, 254 were usable (5%). Birds, mammals, and reptiles each contributed similarly to overall identified prey. Helmeted Guineafowl (Numida meleagris) were the most important bird prey identified (12% of overall prey). The 4 most important mammalian prey species were Thompson's gazelle (Eudorcas thomsonii; 5%), impala (Aepyceros melampus; 4%), common duiker (Sylvicapra grimmia; 4%), and banded mongoose (Mungos mungo; 4%). Reptile prey was dominated by monitor lizards (Varanus spp.; 21%). Prey class proportions differed significantly by regions with mammalian prey being more common in eastern Africa and reptile prey being more common in southern Africa. Within South Africa, reptile prey proportion was greater in the east than in the west. These corroborate existing prey composition studies. Prey composition differed between age classes, with adult eagles preying on more birds than non-adults. There was no significant difference in the average estimated prey weight by eagle age or feeding position (ground, perched, or flying). Our results suggest that this approach may offer a useful method to explore the diet for raptor species that are well photographed across their range, at minimal cost and research effort.
Systemic small vessel vasculitis is associated with antineutrophil cytoplasm antibodies (ANCAs). While there is mounting in vitro evidence to suggest that ANCAs are capable of enhancing ...leukocyte-endothelial interactions, no in vivo evidence for this has been provided. In this study a novel rat model of ANCA-associated experimental autoimmune vasculitis (EAV), induced by immunization with human myeloperoxidase (MPO), was used to analyze directly the potential effect of ANCAs on leukocyte-venular wall interactions in vivo as observed by intravital microscopy. These rats developed anti-MPO antibodies directed against rat leukocytes, showed pathologic evidence of small vessel vasculitis, and had enhanced leukocyte adhesion and transmigration in response to the chemokine Groα (CXCL1 CXC ligand 1). Passive transfer of immunoglobulin from rats with EAV to naive rats conferred enhanced adhesion and transmigration responses in the recipients. Furthermore, rats with EAV and recipients of ANCA-positive immunoglobulin developed extensive microvascular injury, as manifested by mesenteric hemorrhage, in response to CXCL1. This study provides the first direct in vivo evidence for the ability of ANCAs to enhance leukocyteendothelial interactions and cause microvascular hemorrhage, thereby providing a mechanism by which ANCAs could exert pathogenic effects in systemic vasculitis. (Blood. 2005;106:2050-2058)
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