Azithromycin Improves Macrophage Phagocytic Function and Expression of Mannose Receptor in Chronic Obstructive Pulmonary Disease

Hodge, Sandra; Hodge, Greg; Jersmann, Hubertus; Matthews, Geoffrey M.; Ahern, Jessica; Holmes, Mark; Reynolds, Paul N.

doi:10.1164/rccm.200711-1666oc

Cited by 232 publications

(234 citation statements)

References 26 publications

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“…Of interest, this increase in phagocytosis measurement was associated with MR upregulation. 38 However, when comparing the enhancing effect of IL-4 on phagocytosis shown in this study to that of azithromycin reported in another study 38 the IL-4 effect is less than that of azithromycin. The increase is <2 fold vs. 2-4 fold respectively.…”

Section: Discussioncontrasting

confidence: 42%

Macrophages from Patients with Cirrhotic Ascites Showed Function Alteration of Host Defense Receptor

Ahmed

Kadaru

Omer

et al. 2014

Journal of Clinical and Experimental Hepatology

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Background: Patients with cirrhotic ascites (PCA) are susceptible to spontaneous bacterial peritonitis (SBP) which has increased morbidity and mortality. Since some host defense aspects of peritoneal macrophages (PMv) from PCA are altered this study examined factors related to receptor-mediated phagocytosis. Methods: Twelve PCA were studied. PMɸ were isolated from ascitic fluid (AF) samples removed from these patients. Uptake of mannose receptor (MR)-specific ligand, fluorescein isothiocyanate-mannosylated-bovine serum albumin (FITC-man-BSA), by patients' PMɸ and controls, a human monocytic cell line, was measured pre-and post-IL-4 treatment. Phagocytosis of FITC-labeled yeast particles by patients' PMɸ was measured pre-and post-IL-4 treatment. Fluorescence values were obtained using a spectrofuorometer. MRC1 gene was analyzed in blood samples from PCA and controls, healthy donors, using standard polymerase chain reaction (PCR) technique. Results: Past SBP episode(s) were reported in 58.3% of patients. Mean AF volume analyzed per patient was 1.3L. PMɸ ratio in cell yield was 53.73% (SD 18.1). Mean uptake absorbance of patients' PMv was 0.0841 (SD 0.077) compared to 0.338 (SD 0.34) of controls, P = 0.023. Following IL-4 treatment absorbance increased to 0.297 (SD 0.28) in patients' PMv (P = 0.018 on paired sample t-test), and to 0.532 (SD 0.398 in controls (P = 0.053 on independent sample t-test). Mean phagocytosis absorbance of patients' PMv was 0.1250 (SD 0.032) before IL-4 treatment compared to 0.2300 (SD 0.104) after (P = 0.026). PCR analysis for MRC1 gene was negative in all PCA samples compared to positive results in all controls. Conclusion: Since decreased phagocytosis and MR uptake were enhanced post-IL-4 treatment MR downregulation pre-treatment is plausible. Negative PCR results for MRC1 might suggest an anomaly, but this awaits further ellucidation. These altered host defense findings are relevant to infection pathophysiology, and their relevance to SBP susceptibility in PCA is worth verifying. ( J CLIN EXP HEPATOL 2014;4:279-286)

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Section: Discussioncontrasting

confidence: 42%

Macrophages from Patients with Cirrhotic Ascites Showed Function Alteration of Host Defense Receptor

Ahmed

Kadaru

Omer

et al. 2014

Journal of Clinical and Experimental Hepatology

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“…During resolution of airway inflammation, apoptotic epithelial cells are removed by phagocytosis by alveolar macrophages (a process termed 'efferocytosis'). The pathological concept of failed efferocytosis has been described in regard to a number of lung diseases including pulmonary fibrosis 2 , cystic fibrosis 3 chronic granulomatous disease 4 smokers and patients chronic obstructive pulmonary disease (COPD) [5][6][7][8] .…”

Section: Resultsmentioning

confidence: 99%

“…Bronchoscopy was performed according to expert consensus recommendations for the performance of bronchoscopy for investigative purposes (American Thoracic Society) and as previously reported by us [5][6][7][8] .…”

Section: Flexible Bronchoscopymentioning

confidence: 99%

Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

Hodge

Dean

Hodge

et al. 2011

The Journal of Heart and Lung Transplantation

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Short running title: Decreased efferocytosis and MBL in BOSwith BOS) and 14 healthy controls. Abstract & Manuscript 2Results: In plasma, MBL levels were highly variable (0-17.538 g/mL), but increased in infected subjects vs control (p=0.09) or stable groups (p=0.003). There was a similar increase in UC4 in infected patients and a significant correlation between MBL and UC4. There was no correlation between MBL and time post-transplant. In BAL, MBL levels were less variable (0-73.3 ng/mL) and significantly reduced in patients with BOS vs controls and stable groups. 3Lung transplantation is now recognized as an effective treatment option for a variety of end-stage lung diseases and is associated with improvements in life expectancy and quality of life. However the five-year survival is currently only around 60%, the worst of any solid organ transplant, with death beyond the acute phase being largely due to progressive and treatment refractory airway remodeling (obliterative bronchiolitis, OB) manifest clinically as bronchiolitis obliterans syndrome (BOS). BOS is thought to follow persistent alloreactive, infective, and non-specific epithelial injury with dysregulated epithelial repair 1 . Although the predominant histopathologic finding in patients with OB is of fibro-proliferative small airway obliteration, large airways are also affected with the eventual development of bronchiectasis, leading directly to patient morbidity and mortality.The well-ordered process of apoptosis is important for regulation and maintenance of normal tissue homeostasis. During resolution of airway inflammation, apoptotic epithelial cells are removed by phagocytosis by alveolar macrophages (a process termed 'efferocytosis'). The pathological concept of failed efferocytosis has been described in regard to a number of lung diseases including pulmonary fibrosis 2 , cystic fibrosis 3 chronic granulomatous disease 4 smokers and patients chronic obstructive pulmonary disease (COPD) 5-8 .It is considered that the failed efferocytosis results in a net increase in apoptotic material that may lead to secondary necrosis of this material resulting in increased tissue damage and chronic inflammation. This was clearly shown in our studies of COPD where we found evidence of secondary necrosis (increased lactate dehydrogenase in BAL) and that the increased numbers of apoptotic bronchial epithelial cells negatively correlated with efferocytosis 6,9 . In lung transplant recipients we have also described an accumulation of apoptotic material associated with an increase in the cytotoxic mediator granzyme b in the airways 10,11 .Mannose binding lectin (MBL) is a key mediator of both innate immunity and efferocytosis and is thus likely to be important in protecting against lung tissue damage. In other inflammatory chronic lung diseases including COPD, we have shown reduced levels of MBL that correlated with a defect in the 4 ability of alveolar macrophages to phagocytose apoptotic bronchial epithelial cells (efferocytosis) 8 . We further showed that treatm...

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“…In vitro cell culture and animal models have shown that macro lides possess potent antiinflammatory and immunomodulatory properties (Box 2). 11,12 Rela tive to alveolar macrophages from healthy con trols, those from patients with COPD have decreased ability to phagocytose apoptotic cells (efferocytosis) 14 and pathogenic bacteria. 15 Azithromycin reverses this deficit in efferocyto sis 14 and improves the ability of macrophages from patients with COPD to phagocytose bac teria.…”

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confidence: 99%

Long-term macrolide therapy in chronic obstructive pulmonary disease

Parameswaran

Sethi

2014

CMAJ

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Azithromycin Improves Macrophage Phagocytic Function and Expression of Mannose Receptor in Chronic Obstructive Pulmonary Disease

Abstract: Our findings indicate a novel approach to supplement existing therapies in COPD.

Cited by 232 publications

References 26 publications

Macrophages from Patients with Cirrhotic Ascites Showed Function Alteration of Host Defense Receptor

Macrophages from Patients with Cirrhotic Ascites Showed Function Alteration of Host Defense Receptor

Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

Long-term macrolide therapy in chronic obstructive pulmonary disease

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