Disodium cromoglycate inhibits activation of human inflammatory cells in vitro

Kay, A. B.; Walsh, Garry Michael; Moqbel, Redwan; Macdonald, Angus; Nagakura, Toshikazu; Carroll, Mary; Richerson, Hal B.

doi:10.1016/s0091-6749(87)80183-5

Cited by 187 publications

(66 citation statements)

References 25 publications

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“…DSCG treatment significantly reduces the number of eosinophils in bronchial mucus and BAL fluid [417]. In addition, it has been shown to inhibit the tissue accumulation of eosinophils during the late response to allergen in IgE-sensitized rabbits [483], and to PAF in guinea-pig [484] and human skin [485], as well as eosinophil activation in vitro [486,487].…”

Section: Xanthines and Selective Phosphodiesterase Inhibitorsmentioning

confidence: 99%

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II)

Kroegel¹,

Warner²,

Jc³

et al. 1994

Eur Respir J

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The second part of this review on eosinophils focuses on biological cell functions and surveys the various deleterious mechanisms involved in the eosinophil-dominated inflammatory reaction. It discusses the possible pathogenic role of eosinophils in several eosinophil-related diseases, such as parasitic infections, interstitial lung disorders and bronchial diseases, graft rejection, vasculitic granulomatous disorders, pleural effusion, and bronchogenic tumours.The final section of the article highlights the possible recent pharmacological and future therapeutic approaches in modifying eosinophil recruitment and function. Eur Respir J., 1994, 7, 743-760 This paper is published as a follow-on to "Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part I)"* (Eur Respir J, 1994; 7: 519-543). Biological cell functionsThe eosinophil mediates its effector functions through various distinct cellular mechanisms, namely nonoxidative, oxidative, and humoral mechanisms ( fig. 7). Nonoxidative mechanismsAs mentioned previously, the three basic proteins as well as eosinophil peroxidase (EPO) have toxic properties independent of molecular oxygen species. For instance, major basic protein (MBP) [323], eosinophil cationic protein (ECP) [324] and EPO in the presence of hydrogen superoxide and a halide [99] kill helminthic parasites in vitro. In addition, these proteins are toxic for tumour cells and/or mammalian cells [325], including human pulmonary parenchyma and interstitial matrix [326,327], cultured human lung epithelial cells [328], and guinea-pig respiratory epithelium [252, 253,329]. Furthermore, it has been demonstrated that MBP damages human bronchial epithelium, which consists of desquamation and destruction of ciliated cells [329]. Finally, release of their granule proteins by plateletactivating factor (PAF)-activated intact eosinophils has been shown to imitate the characteristic pathological findings of airway epithelium in asthma [330].In addition to their cytotoxic action, eosinophil cationic proteins at certain subtoxic concentrations also stimulate other inflammatory cells. For instance, MBP and ECP have been shown to degranulate platelets [305], induce histamine release from mast cells and basophils [240, 245,331], as well as superoxide anion generation and lysosomal enzyme release by human neutrophils [264].Finally, eosinophil proteins may affect airway muscle function and hyperresponsiveness. Recent reports investigating the effects of direct intratracheal instillation of purified eosinophil granule proteins on pulmonary function and airway responsiveness in primates [281,332] have shown that MBP induces a dose-related increase in airway responsiveness to inhaled methacholine. In the same model, both MBP and EPO caused a transient bronchoconstriction immediately after instillation, that resolved within 1 h. Interestingly, other eosinophil granular proteins failed to effect airway responsiveness or pulmonary function.Mode of action. The mode of action of these basic proteins is n...

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Section: Xanthines and Selective Phosphodiesterase Inhibitorsmentioning

confidence: 99%

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II)

Kroegel¹,

Warner²,

Jc³

et al. 1994

Eur Respir J

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“…DSCG is a safe and widely used drug for the prevention of bronchial asthma (19 -21). DSCG is known to have effects such as mast cell stabilization and suppression of various inflammatory cells (22)(23)(24). Previous studies have also demonstrated that DSCG has antiviral effects, and there has been a recent report about inhibitory effects on influenza virus in vitro and in vivo (18).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Disodium Cromoglycate on Enhanced Adherence of Haemophilus influenzae to A549 Cells Infected With Respiratory Syncytial Virus

et al. 2009

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Nontypeable Haemophilus influenzae (NTHi) secondary infection often complicates respiratory syncytial virus (RSV) infections. Previous studies have revealed that RSV infections enhance NTHi adherence to airway epithelial cells. In this study, we investigated the effects of disodium cromoglycate (DSCG) and corticosteroids, which are frequently used for the treatment of wheezing often related to RSV infections, on the adherence of NTHi to RSV-infected A549 cells. DSCG inhibited enhanced adherence of NTHi to RSV-infected A549 cells, whereas dexamethasone (Dex) and fluticasone propionate (Fp) did not. DSCG suppressed the expression of ICAM-1, which is one of the NTHi receptors. Furthermore, DSCG exhibited an inhibitory effect on RSV infections. It is suggested that DSCG exerts an anti-RSV effect, and consequently attenuates the expression of NTHi receptors. (Pediatr Res 66: 168-173, 2009) R espiratory syncytial virus (RSV) is one of the major pathogens of upper and lower respiratory tract infections in children. RSV infection at a younger age often involves the lower respiratory tract and is frequently associated with expiratory wheezing, which is referred to as bronchiolitis or wheezy bronchitis, asthma, and pneumonia (1). It is known that RSV infections can be complicated by bacterial superinfections (2-5). Nontypeable Haemophilus influenzae (NTHi) is one of the most common bacteria involved in mixed RSVbacterial bronchopulmonary infections in pediatric patients (2,4). It has long been recognized that a preceding local respiratory viral infection seems to play an important role in the pathogenesis of infections by bacteria, including NTHi. The mechanisms underlying bacterial superinfections include virus-induced local destruction of the epithelium, which compromises the host's physiologic barrier, and virus-induced modulation of the immune response (6). In addition, enhanced bacterial adherence to virus-infected cells is considered an important factor increasing the risk of bacterial superinfections (7).Recent studies demonstrated that some respiratory viruses including RSV lead to both expression of viral glycoproteins and up-regulation of cellular molecules including ICAM-1 (CD54), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and platelet activating factor receptor (PAFr) on the host-cell membrane. Both could serve as bacterial receptors and promote bacterial adhesion to the cells (8 -11). Strategies for preventing interaction between RSV and bacteria may reduce the incidence of secondary bacterial complications of RSV infection.Disodium cromoglycate (DSCG) and corticosteroids, which are recognized as inhalation drugs for the management of bronchial asthma, are also used for the treatment of acute infantile wheezing and exacerbation of asthma that are often related to RSV infections. The effects of these medicines against RSV infections and secondary bacterial complications are not clear. In this study, we investigated the effects of DSCG and corticosteroids on the in vitro inte...

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“…This suggests that steroids have a persisting and possibly permanent inhibitory effect on blood eosinophils. Other drugs have also been found to reduce eosinophil function, including nedocromil sodium (Spry, Kumaraswami & Tai, 1986;Rand et al, 1988), and sodium cromoglycate (Kay et al, 1987); however, so far, steroids have proved to be the most effective.…”

Section: Discussionmentioning

confidence: 99%

The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 on the secretory capacity of human blood eosinophils

Tai

Spry

1990

Clinical and Experimental Immunology

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SUMMARYThe effects of recombinant human GM-CSF and interleukin-3 (IL-3) on human blood eosinophil survival, activation, and secretion were studied. Purified normal density eosinophils from patients with the idiopathic hypereosinophilic syndrome (HES) survived in culture for 7 days (50% viable) in the presence of 50 nM GM-CSF or 50 nm IL-3. Neutrophils did not survive after 4 days. No eosinophils survived in the absence of GM-CSF or IL-3. In two out of five patients studied, the cultured eosinophils became elongated with numerous processes. In all five patients the cells became adherent, but there were no morphological signs of degranulation. Both GM-CSF and IL-3 activated eosinophils, transforming the storage form of eosinophil cationic protein (ECP) into the secreted form. The proportion of activated cells increased from less than 20% to over 50% after 4 days in culture. However, GM-CSF and IL-3 did not induce secretion on their own. On the other hand, when GM-CSF/IL-3-activated eosinophils were exposed to known secretory stimuli, there was a six-fold increase in the amount of ECP released when the cells were stimulated with sepharose coated with C3b, and a two-fold increase when they were stimulated with sepharose-activated whole autologous serum. Eosinophils from patients taking steroids were unable to secrete their granule contents, even though they became activated by GM-CSF and IL-3. A novel finding was that sepharose-activated whole serum was an extremely potent secretory signal for ECP, releasing up to 50% of the total ECP content. These studies showed that GM-CSF and IL-3 prime eosinophil effector function by initiating granule solubilization which is the first step in the secretory event, without affecting the subsequent extracellular release of granule proteins.

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Disodium cromoglycate inhibits activation of human inflammatory cells in vitro

Cited by 187 publications

References 25 publications

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II)

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II)

The Effects of Disodium Cromoglycate on Enhanced Adherence of Haemophilus influenzae to A549 Cells Infected With Respiratory Syncytial Virus

The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 on the secretory capacity of human blood eosinophils

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