scholarly journals Leukotriene Receptor Antagonists in the Treatment of Asthma: Implications for Eosinophilic Inflammation

1999 ◽  
Vol 6 (5) ◽  
pp. 453-457 ◽  
Author(s):  
Redwan Moqbel
Keyword(s):  
Basic Protein ◽  
De Novo ◽  
Platelet Activating Factor ◽  
Lipid Mediators ◽  
Eosinophilic Inflammation ◽  
Major Basic Protein ◽  
Receptor Antagonists ◽  
Asthmatic Patients ◽  
Sputum Eosinophils ◽  
Leukotriene Receptor

Recent advances in the treatment and management of asthma have suggested that leukotriene (LT) receptor antagonists may be very beneficial as a second generation therapy with steroid-sparing properties and negligible side effects. These agents have shown interesting effects on peripheral blood and sputum eosinophils. A major contributor to the damage in the airway of asthmatic patients is the eosinophil, which, upon activation, releases a battery of granule-associated cytotoxic, cationic proteins, including the major basic protein and eosinophil peroxidase, and membrane-derived de novo-synthesized bioactive lipid mediators, including LTC4, LTD4and LTE4, as well as platelet activating factor. These products have deleterious effects on the airway tissue including mucosal and smooth muscle layers. Accumulating evidence suggests that these agents may also influence the accumulation and maintenance of eosinophilic responses at the site of inflammation. This article reviews the possible anti-inflammatory mode of action of these therapies. It also discusses where there may be a gap in the knowledge regarding the potential direct and indirect effects of LT modifiers on eosinophil function and recruitment.

Interleukin 9 promotes influx and local maturation of eosinophils

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 1035-1042 ◽  
Author(s):  
Jamila Louahed ◽  
Yuhong Zhou ◽  
W. Lee Maloy ◽  
Pyapalli U. Rani ◽  
Christine Weiss ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peritoneal Cavity ◽  
Basic Protein ◽  
Eosinophilic Infiltration ◽  
Eosinophilic Inflammation ◽  
Major Basic Protein ◽  
Tissue Inflammation ◽  
Background Strain ◽  
Interleukin 9

Abstract The interleukin 9 (IL-9) pathway has recently been associated with the asthmatic phenotype including an eosinophilic tissue inflammation. The mechanism by which IL-9 affects eosinophils (eos) is not known. To investigate whether this cytokine has a direct activity on the development of eos and eosinophilic inflammation, a model of thioglycolate-induced peritoneal inflammation was used in IL-9 transgenic (TG5) and background strain (FVB) mice. In this model, a transient eosinophilic infiltration in the peritoneal cavity was observed in FVB mice 12 to 24 hours after thioglycolate injection that coincided with peak IL-5 and IL-9 release. In contrast, TG5 mice developed a massive eosinophilia that persisted at high levels (81% of total cells) even 72 hours after thioglycolate injection. Release of eosinophilic major basic protein (MBP), IL-4, and IL-5 to the peritoneal cavity of these mice was significantly increased when compared with the control FVB strain. To study the mechanism by which IL-9 exerts its effect on eos, bone marrow or peritoneal cells were cultured in the presence of IL-5, IL-9, or their combination in vitro. IL-5 alone was able to generate significant numbers of eos in TG5 but not FVB mice, whereas a combination of IL-5 and IL-9 induced marked eosinophilia in both strains indicating a synergism between these 2 cytokines. These data suggest that IL-9 may promote and sustain eosinophilic inflammation via IL-5–driven eos maturation of precursors.

scholarly journals Leukotriene Receptor Antagonists and Related Compounds

1999 ◽  
Vol 6 (2) ◽  
pp. 189-193 ◽  
Author(s):  
Sally E Wenzel
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
New Drugs ◽  
Beta Agonist ◽  
Physiological Changes ◽  
Receptor Antagonists ◽  
Asthmatic Patients ◽  
Leukotriene Receptor Antagonists ◽  
Mediators Of Inflammation ◽  
Leukotriene Receptor

Leukotrienes (LTs), lipid mediators of inflammation, have proved to be important biochemicals involved in the symptoms and physiological changes of asthma. In the past year and a half, the development of three new drugs that modulate the LT pathway has been completed. The first subclass of these drugs, leukotriene receptor antagonists (LTRA) (zafirlukast and montelukast), blocks the interaction of the cysteinyl form of the LTs with the cell type bearing the receptor. The second subclass, the 5-lipoxygenase (5-LO) inhibitors (zileuton) inhibits the 5-LO enzyme, which prevents the formation of both cysteinyl LTs and LTB4. The LT modulators have shown efficacy in inhibiting the physiological changes occurring after allergen, acetylsalicylic acid and exercise challenge in asthmatics. In addition, they have shown efficacy in improving symptoms, beta-agonist use and forced expiratory volume in 1 s (FEV1) in chronic, ‘day-to-day’ asthma in patients with mild disease. Comparison studies with low doses of inhaled corticosteroids suggest that LT modulators may have similar effects on symptom scores and beta-agonist use, but have lesser effects on FEV1. Finally, emerging data suggest that these drugs are beneficial in decreasing the dose of inhaled corticosteroids necessary to control more moderate to severe asthma. While long term studies will be helpful in determining the ‘disease modifying’ effects of these drugs, data suggest that these drugs are useful in the treatment of a broad range of asthmatic patients.

Platelet-activating factor and the kidney

1986 ◽  
Vol 251 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
D. Schlondorff ◽  
R. Neuwirth
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Biological Activities ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Initial Step ◽  
Renal Physiology ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Isolated Kidney

Platelet-activating factor (PAF) represents a group of phospholipids with the basic structure of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. A number of different cells are capable of producing PAF in response to various stimuli. The initial step of PAF formation is activation of phospholipase A2 in a calcium-dependent manner, yielding lyso-PAF. During this step arachidonic acid is also released and can be converted to its respective cyclooxygenase and lipoxygenase products. The lyso-PAF generated is then acetylated in position 2 of the glycerol backbone by a coenzyme A (CoA)-dependent acetyltransferase. An additional pathway may exist whereby PAF is generated de novo from 1-alkyl-2-acetyl-sn-glycerol by phosphocholine transferase. PAF inactivation in cells and blood is by specific acetylhydrolases. PAF exhibits a variety of biological activities including platelet and leukocyte aggregation and activation, increased vascular permeability, respiratory distress, decreased cardiac output, and hypotension. In the kidney PAF can produce decreases in blood flow, glomerular filtration, and fluid and electrolyte excretion. Intrarenal artery injection of PAF may also result in glomerular accumulation of platelets and leukocytes and mild proteinuria. PAF increases prostaglandin formation in the isolated kidney and in cultured glomerular mesangial cells. PAF also causes contraction of mesangial cells. Upon stimulation with calcium ionophore the isolated kidney, isolated glomeruli and medullary cells, and cultured mesangial cells are capable of producing PAF. The potential role for PAF in renal physiology and pathophysiology requires further investigation that may be complicated by 1) the multiple interactions of PAF, prostaglandins, and leukotrienes and 2) the autocoid nature of PAF, which may restrict its action to its site of generation.

scholarly journals Biochemical and amino acid sequence analysis of human eosinophil granule major basic protein.

1988 ◽  
Vol 263 (25) ◽  
pp. 12559-12563
Author(s):  
T L Wasmoen ◽  
M P Bell ◽  
D A Loegering ◽  
G J Gleich ◽  
F G Prendergast ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sequence Analysis ◽  
Amino Acid Sequence ◽  
Basic Protein ◽  
Major Basic Protein ◽  
Amino Acid Sequence Analysis ◽  
Human Eosinophil ◽  
Eosinophil Granule

scholarly journals A Novel and Highly Divergent Homolog of Human Eosinophil Granule Major Basic Protein

1999 ◽  
Vol 274 (20) ◽  
pp. 14464-14473 ◽  
Author(s):  
Douglas A. Plager ◽  
David A. Loegering ◽  
Deborah A. Weiler ◽  
James L. Checkel ◽  
Jill M. Wagner ◽  
...  
Keyword(s):  
Basic Protein ◽  
Major Basic Protein ◽  
Human Eosinophil ◽  
Eosinophil Granule

Normal Saline Solution Nasal-Pharyngeal Irrigation Improves Chronic Cough Associated with Allergic Rhinitis

2017 ◽  
Vol 31 (2) ◽  
pp. 96-104 ◽  
Author(s):  
Lin Lin ◽  
Zhongchun Chen ◽  
Yitan Cao ◽  
Guangbin Sun
Keyword(s):  
Allergic Rhinitis ◽  
House Dust ◽  
House Dust Mite ◽  
Chronic Cough ◽  
Saline Solution ◽  
Basic Protein ◽  
Leukotriene C4 ◽  
Major Basic Protein ◽  
Leicester Cough Questionnaire ◽  
Dust Mite

Background Upper airway inflammation is one of the most commonly identified causes of chronic cough, although the underlying mechanism is not clear. This study compared normal saline solution nasal-pharyngeal irrigation (NSNPI) and fluticasone propionate nasal spray (FPNS) treatment for chronic cough associated with allergic rhinitis (AR). Methods Patients with suspected AR to house-dust mite were enrolled, and the symptom of cough was assessed by a cough symptom score and the Leicester Cough Questionnaire, and cough response to capsaicin was evaluated. AR was assessed by using the visual analog scale (VAS) and the Mini Juniper Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Mediators, including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein from nasal lavage fluid (NLF) were examined. The patients were treated with NSNPI (the NSNPI group) or FPNS (the FPNS group) for 30 days, after which they were reassessed. Results Forty-five of 50 patients completed this study. The scores of the cough symptom and the Leicester Cough Questionnaire, and the capsaicin cough threshold all improved statistically after NSNPI but did not change after FPNS. There were statistically significant changes in the evaluations of the MiniRQLQ and the mediators, including histamine and leukotriene C4, in the NLF in the NSNPI group. However, significant changes were found in the assessments of VAS, MiniRQLQ, and all above mediators including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein in the NLF of the FPNS group. Furthermore, the assessments of VAS and all the mediators were reduced more in the FPNS group compared with those in the NSNPI group. Conclusion The patients with suspected AR to house-dust mite reported a better relief of the cough symptom after 30 days of treatment with NSNPI compared with that after nasal corticosteroid.

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