scholarly journals Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

2010 ◽  
Vol 78 (10) ◽  
pp. 4320-4330 ◽  
Author(s):  
Heather M. Kling ◽  
Timothy W. Shipley ◽  
Sangita P. Patil ◽  
Jan Kristoff ◽  
Marianne Bryan ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Hiv Infection ◽  
Pulmonary Disease ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Primate Model ◽  
Pneumocystis Jiroveci ◽  
Obstructive Pulmonary Disease ◽  
Specific Memory ◽  
Shiv Infection

ABSTRACT Pulmonary colonization by the opportunistic pathogen Pneumocystis jiroveci is common in HIV+ subjects and has been associated with development of chronic obstructive pulmonary disease (COPD). Host and environmental factors associated with colonization susceptibility are undefined. Using a simian-human immunodeficiency virus (SHIV) model of HIV infection, the immunologic parameters associated with natural Pneumocystis jiroveci transmission were evaluated. SHIV-infected macaques were exposed to P. jiroveci by cohousing with immunosuppressed, P. jiroveci-colonized macaques in two independent experiments. Serial plasma and bronchoalveolar lavage (BAL) fluid samples were examined for changes in antibody titers to recombinant Pneumocystis-kexin protein (KEX1) and evidence of Pneumocystis colonization by nested PCR of BAL fluid. In experiment 1, 10 of 14 monkeys became Pneumocystis colonized (Pc+) by 8 weeks post-SHIV infection, while 4 animals remained Pneumocystis colonization negative (Pc−) throughout the study. In experiment 2, 11 of 17 animals became Pneumocystis colonized by 16 weeks post-SHIV infection, while 6 monkeys remained Pc−. Baseline plasma KEX1-IgG titers were significantly higher in monkeys that remained Pc−, compared to Pc+ monkeys, in experiments 1 (P = 0.013) and 2 (P = 0.022). Pc− monkeys had greater percentages of Pneumocystis-specific memory B cells after SHIV infection compared to Pc+ monkeys (P = 0.037). After SHIV infection, Pc+ monkeys developed progressive obstructive pulmonary disease, whereas Pc− monkeys maintained normal lung function throughout the study. These results demonstrate a correlation between the KEX1 humoral response and the prevention of Pneumocystis colonization and obstructive lung disease in the SHIV model. In addition, these results indicate that an effective Pneumocystis-specific memory B-cell response is maintained despite progressive loss of CD4+ T cells during SHIV infection.

scholarly journals Association of Functional Variants of Phase I and II Genes with Chronic Obstructive Pulmonary Disease in a Serbian Population / Udruženost Funkcionalnih Varijanti Gena Faze I I Ii Sa Hroničnom Opstruktivnom Bolešću Pluća U Srpskoj Populaciji

2015 ◽  
Vol 34 (2) ◽  
pp. 207-214 ◽  
Author(s):  
Marija Stanković ◽  
Aleksandra Nikolić ◽  
Andrija Tomović ◽  
Marija Mitić-Milikić ◽  
Ljudmila Nagorni-Obradović ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Phase I ◽  
Pulmonary Disease ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Functional Variants ◽  
Copd Patients ◽  
Phase I And Ii

Summary Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants-antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population. Methods: The genotypes of 122 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A/*2A, CYP2E1 *1A/*5B, GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants. Results: Results obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; OR=1.80; p=0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; OR=1.98; p=0.029), as well as for CYP1A1 *1A/*2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; OR=7.88; p=0.025). Conclusions: These are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far.

scholarly journals Role of Apoptotic Cell Clearance in Pneumonia and Inflammatory Lung Disease

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 134
Author(s):  
David Jiao Zheng ◽  
Maria Abou Taka ◽  
Bryan Heit
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Inflammatory Diseases ◽  
Apoptotic Cell ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Obstructive Pulmonary Disease ◽  
Cell Clearance

Pneumonia and inflammatory diseases of the pulmonary system such as chronic obstructive pulmonary disease and asthma continue to cause significant morbidity and mortality globally. While the etiology of these diseases is highly different, they share a number of similarities in the underlying inflammatory processes driving disease pathology. Multiple recent studies have identified failures in efferocytosis—the phagocytic clearance of apoptotic cells—as a common driver of inflammation and tissue destruction in these diseases. Effective efferocytosis has been shown to be important for resolving inflammatory diseases of the lung and the subsequent restoration of normal lung function, while many pneumonia-causing pathogens manipulate the efferocytic system to enhance their growth and avoid immunity. Moreover, some treatments used to manage these patients, such as inhaled corticosteroids for chronic obstructive pulmonary disease and the prevalent use of statins for cardiovascular disease, have been found to beneficially alter efferocytic activity in these patients. In this review, we provide an overview of the efferocytic process and its role in the pathophysiology and resolution of pneumonia and other inflammatory diseases of the lungs, and discuss the utility of existing and emerging therapies for modulating efferocytosis as potential treatments for these diseases.

scholarly journals Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target

2021 ◽  
Vol 8 ◽  
Author(s):  
Srikanth Karnati ◽  
Michael Seimetz ◽  
Florian Kleefeldt ◽  
Avinash Sonawane ◽  
Thati Madhusudhan ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Nitrosative Stress ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Cor Pulmonale ◽  
Present Review ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and encompasses chronic bronchitis and emphysema. It has been shown that vascular wall remodeling and pulmonary hypertension (PH) can occur not only in patients with COPD but also in smokers with normal lung function, suggesting a causal role for vascular alterations in the development of emphysema. Mechanistically, abnormalities in the vasculature, such as inflammation, endothelial dysfunction, imbalances in cellular apoptosis/proliferation, and increased oxidative/nitrosative stress promote development of PH, cor pulmonale, and most probably pulmonary emphysema. Hypoxemia in the pulmonary chamber modulates the activation of key transcription factors and signaling cascades, which propagates inflammation and infiltration of neutrophils, resulting in vascular remodeling. Endothelial progenitor cells have angiogenesis capabilities, resulting in transdifferentiation of the smooth muscle cells via aberrant activation of several cytokines, growth factors, and chemokines. The vascular endothelium influences the balance between vaso-constriction and -dilation in the heart. Targeting key players affecting the vasculature might help in the development of new treatment strategies for both PH and COPD. The present review aims to summarize current knowledge about vascular alterations and production of reactive oxygen species in COPD. The present review emphasizes on the importance of the vasculature for the usually parenchyma-focused view of the pathobiology of COPD.

scholarly journals Chronic obstructive pulmonary disease and HIV-infection

2021 ◽  
Vol 12 (4) ◽  
pp. 23-31
Author(s):  
I. B. Viktorova ◽  
V. N. Zimina ◽  
A. V. Kravchenko
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Hiv Infection ◽  
Pulmonary Disease ◽  
Mutual Influence ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Economic Significance ◽  
Lung Condition ◽  
Infectious Disease Specialists ◽  
Clinically Significant

The increasing life expectancy of HIV-infected persons due to antiretroviral therapy (ART) is associated with growing frequency of non-opportunistic respiratory diseases. This review of literature is devoted to chronic obstructive pulmonary disease (COPD), which is known to be the most common chronic noninfectious lung condition in HIV-patients. The prevalence of COPD in the global population with HIV is high and is associated with HIV.The article contains actual data on HIV/COPD comorbidity, presents current information on mechanism of COPD development in HIV-infection, factors contributing to the mutual influence and adverse course of comorbid conditions. The specialties of COPD treatment during ART and clinically significant drug interactions between different COPD medications and some antiretrovirals are highlighted.The socio-economic significance of both HIV-infection and COPD argues wide informing of pulmonologists, therapists and infectious disease specialists about the course and treatment of COPD in persons with HIV-infection.

scholarly journals Comparison of arterial and venous blood biomarker levels in chronic obstructive pulmonary disease

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 114 ◽  
Author(s):  
Emer Kelly ◽  
Caroline A Owen ◽  
Amadeus Abraham ◽  
David L Knowlton ◽  
Bartolome R Celli ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Venous Blood ◽  
Normal Lung ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Blood Samples ◽  
Arterial Blood ◽  
Significant Difference

Purpose: The development of novel biomarkers is an unmet need in chronic obstructive pulmonary disease (COPD). Arterial blood comes directly from the lung and venous blood drains capillary beds of the organ or tissue supplied. We hypothesized that there would be a difference in levels of the biomarkers metalloproteinase 9 (MMP-9), vascular endothelial growth factor A (VEGF-A) and interleukin 6 (IL-6) in arterial compared with venous blood. Methods: Radial artery and brachial vein blood samples were taken simultaneously in each of 12 patients with COPD and seven controls with normal lung function. Circulating immunoreactive MMP-9, VEGF-A and IL-6 levels in serum were measured using quantitative enzyme-linked immunosorbent assays. Results were compared using a Student’s paired t test. The study was powered to determine whether significant differences in cytokine levels were present between paired arterial and venous blood samples.  Results: In the 12 patients with COPD, four were female, and age ranged 53-85 years, mean age 69 years. Three patients in the control group were female, with age range 46-84 years, mean age 64.7 years. In the COPD group, three patients had mild, five moderate and four severe COPD. No significant difference was found between arterial and venous levels of MMP-9, VEGF-A or IL-6. Conclusions: In this pilot study, levels of the measured biomarkers in arterial compared with venous blood in both COPD patients and healthy controls did not differ. This suggests that as we continue to chase the elusive biomarker in COPD as a potential tool to measure disease activity, we should focus on venous blood for this purpose.

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