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1.  Increase in Net Activity of Serine Proteinases but Not Gelatinases after Local Endotoxin Exposure in the Peripheral Airways of Healthy Subjects 
PLoS ONE  2013;8(9):e75032.
We tested the hypothesis that activation of the innate immune response induces an imbalance in the proteolytic homeostasis in the peripheral airways of healthy subjects, towards excess serine or gelatinase proteinase activity. During bronchoscopy, 18 healthy human subjects underwent intra-bronchial exposure to endotoxin and contra-lateral exposure to vehicle. Bronchoalveolar lavage (BAL) samples were harvested 24 or 48 hours (h) later. We quantified archetype proteinases, anti-proteinases, inflammatory BAL cells, and, importantly, total plus net proteinase activities using functional substrate assays. As expected, endotoxin exposure increased the concentrations of polymorphonuclear leukocytes (PMN's) and macrophages, of proteinases and the anti-proteinases tissue inhibitor of metalloproteinase-1, α-1-antitrypsin and, to a lesser extent, secretory leukoproteinase inhibitor, at both time points. Notably, at these time points, endotoxin exposure substantially increased the quantitative NE/SLPI ratio and the net serine proteinase activity corresponding to neutrophil elastase (NE). Endotoxin exposure also increased the total gelatinase activity corresponding to matrix metalloproteinase (MMP)-9; an activity dominating over that of MMP-2. However, endotoxin exposure had no impact on net gelatinolytic activity at 24 or 48 h after exposure. Thus, local activation of the innate immune response induces an imbalance towards increased net serine proteinase activity in the proteolytic homeostasis of the peripheral airways in healthy subjects. Hypothetically, this serine proteinase activity can contribute to tissue remodelling and hypersecretion via NE from PMN's, if it is triggered repeatedly, as might be the case in chronic inflammatory airway disorders.
doi:10.1371/journal.pone.0075032
PMCID: PMC3781029  PMID: 24086430
2.  Activated Human T Cells Secrete Exosomes That Participate in IL-2 Mediated Immune Response Signaling 
PLoS ONE  2012;7(11):e49723.
It has previously been shown that nano-meter sized vesicles (30–100 nm), exosomes, secreted by antigen presenting cells can induce T cell responses thus showing the potential of exosomes to be used as immunological tools. Additionally, activated CD3+ T cells can secrete exosomes that have the ability to modulate different immunological responses. Here, we investigated what effects exosomes originating from activated CD3+ T cells have on resting CD3+ T cells by studying T cell proliferation, cytokine production and by performing T cell and exosome phenotype characterization. Human exosomes were generated in vitro following CD3+ T cell stimulation with anti-CD28, anti-CD3 and IL-2. Our results show that exosomes purified from stimulated CD3+ T cells together with IL-2 were able to generate proliferation in autologous resting CD3+ T cells. The CD3+ T cells stimulated with exosomes together with IL-2 had a higher proportion of CD8+ T cells and had a different cytokine profile compared to controls. These results indicate that activated CD3+ T cells communicate with resting autologous T cells via exosomes.
doi:10.1371/journal.pone.0049723
PMCID: PMC3500321  PMID: 23166755
3.  A gender difference in circulating neutrophils in malnourished patients with COPD 
Background
Circulating markers of inflammation in chronic obstructive pulmonary disease (COPD) may correlate to disease progression and extrapulmonary complications such as malnourishment. However, surprisingly little is known about gender-related differences for circulating inflammatory markers in COPD.
Purpose
To characterize differences in circulating markers of inflammation in malnourished female and male patients with COPD.
Subjects
Thirty female and 11 male patients with a clinical diagnosis of COPD and malnourishment were examined. A group of control subjects without evidence of COPD was recruited for comparison of some variables.
Methods
Blood samples were drawn, and the following parameters were studied: leukocytes and differential counts, C-reactive protein (CRP), tumor necrosis factor-α, interleukin (IL)-6 and IL-8, myeloperoxidase (MPO), neutrophil elastase (NE), intracellular adhesion molecule-1, vascular endothelial adhesion molecule-1, and E-selectin.
Results
The mean neutrophil concentration was significantly (P = 0.019) higher in female (4.5 × 109/L) than in male patients with COPD (3.5 × 109/L) and significantly higher than in female control subjects (3.1 × 109/L) (P < 0.01, n = 85). The mean CRP values were considerably higher in female (4.9 mg/mL) than in male patients with COPD (1.5 mg/mL), but the difference was not statistically significant (P = 0.20). The mean concentrations of IL-6 and IL-8 tended to be higher in female than in male patients with COPD, but these differences did not reach statistical significance either (P > 0.05). Confounding factors (smoking, medication) could not explain the gender differences noted. The concentrations of MPO and NE displayed a strong correlation (r = 0.89; P < 0.01, n = 41) but revealed no gender differences. The latter was true for concentrations of adhesion molecules as well.
Conclusions
Our study puts forward evidence of a gender-related difference in systemic inflammation in malnourished patients with COPD in terms of circulating neutrophils being more abundant in female patients. Among these female patients, there was also a trend toward an increase in two neutrophil-mobilizing cytokines. New and better-powered studies are warranted to confirm and characterize this potentially important phenomenon in greater detail.
doi:10.2147/COPD.S15351
PMCID: PMC3048083  PMID: 21407820
chronic obstructive pulmonary disease; inflammatory markers; leukocytosis; malnutrition

Results 1-3 (3)