Natural Porcine Surfactant Augments Airway Inflammation after Allergen Challenge in Patients with Asthma

Erpenbeck, Veit J.; Hagenberg, Andreas; Dulkys, Yasmin; Elsner, Jörn; Bälder, Ralf; Krentel, Harald; Discher, Marc; Braun, Armin; Krug, Norbert; Hohlfeld, Jens M.

doi:10.1164/rccm.200301-104oc

Cited by 48 publications

(55 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Babu et al (1) showed that pulmonary surfactant dysfunction may also contribute to the very early asthmatic response to allergen and that exogenous surfactant administration could serve as a useful adjunct in controlling the early allergen-induced symptoms in patients with allergic asthma. Other studies raise concerns over the use of surfactant replacement materials sourced from animals, suggesting species differences in biochemistry and function of surfactant and highlighting a lack of understanding of the surfactant system (10). Inhibition or overload of the surfactant system by urban PM inhalation and surfactant sequestration may therefore be related to the observed health effects of PM exposure, such as increased infections in PM exposed rats (41) and PM exposed humans (9,27).…”

Section: Discussionmentioning

confidence: 99%

Fine airborne urban particles (PM_2.5) sequester lung surfactant and amino acids from human lung lavage

Kendall¹

2007

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Kendall M. Fine airborne urban particles (PM2.5) sequester lung surfactant and amino acids from human lung lavage. Am J Physiol Lung Cell Mol Physiol 293: L1053-L1058, 2007. First published July 6, 2007; doi:10.1152/ajplung.00131.2007.-Components of surfactant act as opsonins and enhance phagocytosis of bacteria; whether this process occurs with atmospheric fine particles has not been shown. We have studied the interactions of fine particles (urban PM2.5) and surfactant removed from normal human lungs by lavage, using a surface analysis technique. The aim was to identify which of the chemical components of brochoalveolar lavage (BAL) deposit on the surfaces of urban PM 2.5. Deposition of surfactant components on urban PM2.5 surfaces was reported in previous studies, but molecular identification and relative quantification was not possible using simple data analysis. In this study, we were able to identify adsorbed components by applying an appropriate statistical technique, factor analysis. In this study, the most strongly associated mass fragment on PM2.5 surfaces exposed to BAL (and undetected on both untreated samples and saline controls) was di-palmitoyl-phosphatidylcholine, a component of lung surfactant. Amino acids were also strongly associated with BAL-exposed PM2.5 surfaces and not other sample types. Thirteen mass fragments were identified, diagnostic of the amino acids alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, serine, and valine. This study provides evidence that lung surfactant and amino acids related to opsonin proteins adsorb to nonbiological particle surfaces exposed to human lung lining fluid. Disruption of normal surfactant function, both physical and immunological, is possible but unproven. Further work on this PM-opsonin interaction is recommended. bronchoalveolar lavage EPIDEMIOLOGICAL STUDIES have shown that exposure to particulate air pollutants damages health (32). The exact mechanisms further underlying these air pollution effects remain unknown, although recent work (29, 39) has shown that cardiovascular system (acutely) and the developing respiratory system (chronic effects; Ref. 11) are most significantly affected. Effects on the cardiovascular system were seen on the day of exposure, indicating immediate short-term effects that were detectable within hours of exposures. It is likely that sensitivity to particles varies across the population with the young, the elderly, and those with preexisting cardio-respiratory disease being most at risk (31). Effects occur at ambient concentrations in industrial countries: These concentrations are low compared with concentrations recorded in earlier periods and with those common, now, in developing countries (8). Epidemiological and toxicological studies have demonstrated associations between specific PM characteristics and increased mortality and morbidity. Implicated characteristics include surface area, metals, acidic components, oxidative stress potent...

show abstract

Section: Discussionmentioning

confidence: 99%

Fine airborne urban particles (PM_2.5) sequester lung surfactant and amino acids from human lung lavage

Kendall¹

2007

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…The instilled amount of antigen was 10–1,000 SQ-U diluted in 10 ml of saline solution. Bronchial hyperresponsiveness and the provocative concentration of methacholine that reduced forced expiratory volume in 1 s by 20% (PC 20 ) were determined as described [25]. Patients only used salbutamol when required for relief of symptoms.…”

Section: Methodsmentioning

confidence: 99%

Regulation of GATA-3, c-maf and T-bet mRNA Expression in Bronchoalveolar Lavage Cells and Bronchial Biopsies after Segmental Allergen Challenge

Erpenbeck¹,

Hagenberg²,

Krentel³

et al. 2006

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

Background: GATA-3 (GATA binding protein 3) and the proto-oncogene c-maf are Th2-regulating transcription factors that control the expression of interleukin (IL)-4 and IL-5, while T-bet (T-box expressed in T cells) is a Th1-specific transcription factor that controls the expression of interferon (IFN-γ). Allergen provocation in asthmatics induces a Th2-dominated cytokine profile, but so far it is unknown whether the skewed cytokine expression is reflected by the expression of the respective transcriptional regulators. Objective: The aim of this study was to determine the regulation of Th1- and Th2-specific transcription factors and cytokines in 10 atopic subjects with mild asthma and 5 nonatopic healthy controls at baseline and after segmental sham and allergen challenge. Methods: The mRNA expression of GATA-3, c-maf and T-bet was determined by real-time polymerase chain reaction in bronchoalveolar lavage (BAL) cells and bronchial biopsies. The percentage of IL-4+, IL-5+ and IFN-γ+ BAL T cells was determined by flow cytometry, and BAL levels of these cytokines were measured by ELISA. Results: In BAL cells of asthmatics, the mRNA expression of all transcription factors was increased after allergen challenge. In bronchial biopsies, the basal expression of GATA-3 was increased in asthmatics compared to healthy controls but decreased after allergen challenge. Compared to sham challenge, the percentage of IL-5+/CD4+ BAL T cells was increased after allergen challenge in asthmatics while the percentage of IFN-γ+/CD4+ and IFN-γ+/CD8+ T cells was decreased. Expression of c-maf mRNA in BAL cells correlated with IL-4+/CD4+ BAL cells and BAL IL-5 levels. Conclusions: Segmental allergen challenge in asthmatics leads to increased GATA-3, c-maf and T-bet expression in BAL cells but not in bronchial biopsies.

show abstract

“…To determine the allergen dose for the segmental instillation, a skinprick test with a dilution series of the allergen extract in saline was done as previously described (26). The allergen concentration that elicited at least a 3-mm-diameter skin weal response was selected for instillation (100-100.000 SQE diluted in 10 ml saline).…”

Section: Dosage and Preparation Of Challenge Substancesmentioning

confidence: 99%

Endotoxin Augments Myeloid Dendritic Cell Influx into the Airways in Patients with Allergic Asthma

Schaumann¹,

Müller²,

Braun³

et al. 2008

Am J Respir Crit Care Med

Self Cite

View full text Add to dashboard Cite

Rationale: Epidemiologic studies have shown that exacerbation of asthma is modulated by environmental endotoxin. High levels of endotoxin are associated with asthma symptoms and the current use of asthma medication. However, the underlying mechanisms by which endotoxin modulates asthma are not completely understood. Objectives: The aim of the study was to test whether endotoxin enhances the response of individuals with allergic asthma to allergen, and to determine if this interaction is associated with increased numbers of antigen-presenting cells in the airways. Methods: Seventeen subjects with mild allergic asthma underwent segmental challenge with allergen, endotoxin, and the combination of both in three different lung segments via bronchoscopy. The cellular influx including monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), as well as the level of cytokines, were assessed in bronchoalveolar lavage fluid obtained 24 hours after segmental challenge. Monocytes, mDCs, and pDCs were isolated and their capacity to induce T cell proliferation was determined. Measurements and Main Results: Endotoxin enhanced the cellular response to allergen. The combination of allergen and endotoxin resulted in increased numbers of total cells, lymphocytes, neutrophils, eosinophils, monocytes, and mDCs, as well as increased levels of lipopolysaccharide-binding protein, IL-1a, IL-6, and tumor necrosis factor-a in the bronchoalveolar lavage fluid compared with allergen alone. Isolated mDCs but not pDCs induced a strong T cell proliferation in vitro. Conclusions: Endotoxin augments the allergic inflammation in the lungs of individuals with asthma, and induces an enhanced influx of monocytes and functionally active antigen-presenting mDCs into the respiratory tract.

show abstract

Natural Porcine Surfactant Augments Airway Inflammation after Allergen Challenge in Patients with Asthma

Cited by 48 publications

References 37 publications

Fine airborne urban particles (PM_2.5) sequester lung surfactant and amino acids from human lung lavage

Fine airborne urban particles (PM_2.5) sequester lung surfactant and amino acids from human lung lavage

Regulation of GATA-3, c-maf and T-bet mRNA Expression in Bronchoalveolar Lavage Cells and Bronchial Biopsies after Segmental Allergen Challenge

Endotoxin Augments Myeloid Dendritic Cell Influx into the Airways in Patients with Allergic Asthma

Contact Info

Product

Resources

About