Erythromycin Inhibits Respiratory Glycoconjugate Secretion from Human Airways<i>In Vitro</i>

Goswami, Satindra; Kivity, Shmuel; Marom, Zvi

doi:10.1164/ajrccm/141.1.72

Cited by 204 publications

(92 citation statements)

References 10 publications

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“…By using the same adherence model and SEM assessment for bacterial adherence density, it was shown recently by the authors that PA specifically adhere to human basement membrane collagen via recognition of the b-Dgalactose-1-4-b-D-N-acetylglucosamine sequence on type IV collagen and this process could be inhibited by heparin and Ca 2z [17]. Administration of low-dose EM, probably by the inhibition of glycoconjugate release [18], reduces sputum production in patients with bronchorrhoea [19] and DPB [7,9]. Low-dose EM, with unclear mechanisms, also reduces airway responsiveness in patients with bronchiectasis [20].…”

Section: Discussionmentioning

confidence: 98%

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Tsang¹,

Ng²,

Ho³

et al. 2003

Eur Respir J

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The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised by Pseudomonas aeruginosa (PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis.In this study, an in vitro model to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,0006) when PA was cultured in 0.05, 0.5 and 5 mg?mL -1 of EM compared with control (absence of EM). Adherence density (20 SEM fields?log -1 inocular size) for PA obtained from no EM (56.8¡43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 mg?mL -1 EM (21.5¡17.56, 23.3¡16.65, and 21.4¡12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 mg?mL -1 ) had a significant reduction in its diagonal length, radius, height, volume and surface area.It is possible, therefore, that these misshaped Pseudomonas aeruginosa bacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airway in vivo. Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients with Pseudomonas aeruginosa infection. Eur Respir J 2003; 21: 401-406.

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Section: Discussionmentioning

confidence: 98%

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Tsang¹,

Ng²,

Ho³

et al. 2003

Eur Respir J

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“…However, erythromycin exerts someeffect on PMNs,as a neutrophil chemotactic factor is reportedly reduced in the bronchoalveolar lavage fluid of patients with DPBfollowing its administration (24). Erythromycin suppresses the secretion of mucusand water fromthe airway membranes (25,26), and inhibits activated T lymphocytes (27), as well as enhances the proliferation and differentiation of the progenitors of macrophages (28). Future studies of the immunomodulating effects of the 14-membered ring macrolides should focus on the mechanismof the efficacy in treating DPB.…”

Section: Discussionmentioning

confidence: 99%

Effect of 14-Membered Ring Macrolide Therapy on Chronic Respiratory Tract Infections and Polymorphonuclear Leukocyte Activity.

1995

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“…Although the mechanisms are uncertain, macrolides may exert these effects through actions other than their antimicrobial properties, such as immunomodulatory actions on inflammatory cells [13], reduction of airway secretion [14] and inhibition of cholinergic neurotransmission [15]. Because overproduction of NO by type II NOS may be associated with the development of airway inflammation, it was hypothesized that macrolides could affect the NO-generating system in inflammatory cells.…”

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confidence: 99%

Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages

Kohri¹,

Tamaoki²,

Kondo³

et al. 2000

Eur Respir J

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There is evidence that macrolide antibiotics are effective in the treatment of chronic airway inflammatory diseases, probably through actions other than their antibacterial properties.In order to determine whether macrolides affect the nitric oxide-generating system in the respiratory tract, rat pulmonary alveolar macrophages (PAMs) were studied in vitro. The release of NO was assessed by direct measurement with a specific amperometric sensor for this molecule, and the expression of type II NO synthase (NOS) messenger ribonucleic acid (mRNA) was determined by Northern blotting.Incubation of PAMs with lipopolysaccharide from Escherichia coli and recombinant human interferon-gamma caused release of NO, which was accompanied by induction of type II NOS mRNA. The release of NO was reduced by coincubation of cells with the macrolides erythromycin, clarithromycin and josamycin in a concentration-dependent manner, the maximal inhibition being 7310, 816 and 849%, respectively, but was not altered by amoxycillin or cefaclor. These macrolides likewise inhibited the induction of type II NOS mRNA, whereas no inhibitory effects were observed with amoxycillin or cefaclor.These results suggest that macrolide antibiotics specifically inhibit type II NO synthase gene expression and consequently reduce NO production by rat pulmonary alveolar macrophages, which might result in attenuation of airway inflammation. Eur Respir J 2000; 15: 62±67. Nitric oxide is a highly reactive gaseous free radical generated from the amino acid L-arginine by NO synthase (NOS), which exists in both constitutive and inducible isoforms [1,2]. Endogenous NO may be involved in the regulation of airway and vascular smooth muscle tone, microvascular permeability, pulmonary neurotransmission and host defence [3]. Moreover, NO may have antiinflammatory effects, such as protection against vascular leakage, leukocyte adherence and cellular damage [4,5]. However, NO can exert deleterious effects when it is inappropriately generated or overproduced, and excessive amounts of NO and its metabolites such as peroxynitrite may contribute to the pathophysiology of inflammation and the resultant tissue damage [3,6,7]. In the respiratory tract, the existence of constitutive form of NOS (type I and type III NOS) has been shown in various cell types, including vascular endothelial cells, nerve cells and airway epithelial cells [8], indicating that these cells constitutively generate NO. Conversely, production of NO is upregulated in a variety of pulmonary inflammatory diseases [9±11], in which inducible NOS (type II NOS) in pulmonary alveolar macrophages (PAMs) may be involved.There is some evidence to suggest that long-term administration of the macrolide antibiotic agent erythromycine may be effective in the treatment of chronic airway inflammation, including chronic bronchitis, bronchiectasis and diffuse panbronchiolitis [12,13]. Although the mechanisms are uncertain, macrolides may exert these effects through actions other than their antimicrobial properties,...

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Erythromycin Inhibits Respiratory Glycoconjugate Secretion from Human AirwaysIn Vitro

Cited by 204 publications

References 10 publications

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Effect of 14-Membered Ring Macrolide Therapy on Chronic Respiratory Tract Infections and Polymorphonuclear Leukocyte Activity.

Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages

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