Abstract:
RATIONALE:Neutrophils are key players in chronic obstructive pulmonary disease (COPD), and increased numbers of neutrophils are present in sputum and lung tissue of patients with COPD. Interestingly, immunoglobulin free light chains (IgLC) are able to prolong the life of neutrophils; therefore, IgLC may contribute to the chronic state of inflammation. OBJECTIVES:In this study, the relation between IgLC and COPD has been investigated. METHODS:We investigated the presence of IgLC in different murine lung emphysema models. IgLC levels in serum from mice and patients with COPD were examined by Western blot analysis and ELISA, respectively. IgLC levels in lung tissue were determined by immunohistochemistry. Fluorescence-activated cell sorter and immunofluorescent analysis were used to detect binding between IgLC and human neutrophils. Interleukin-8 (CXCL8) release by neutrophils after IgLC incubation was measured by ELISA. The effect of F991, an IgLC antagonist, was examined on the neutrophil influx in murine lungs after 5 days of smoke exposure. MEASUREMENTS AND MAIN RESULTS:Increased levels of IgLC in serum of cigarette smoke-exposed and cigarette smoke extract-treated mice compared with control mice were observed. Patients with COPD showed increased serum IgLC and expression of IgLC in lung tissue compared with healthy volunteers. Interestingly, IgLC bound to neutrophils and activated neutrophils to release CXCL8. F991 inhibited the IgLC binding to neutrophils and reduced the smoke-induced neutrophil influx in murine lungs after smoke exposure. CONCLUSIONS:This study describes for the first time an association between neutrophils and IgLC in the pathophysiology of COPD, which could open new avenues to targeted treatment of this chronic disease.
journal_name
Am J Respir Crit Care Medauthors
Braber S,Thio M,Blokhuis BR,Henricks PA,Koelink PJ,Groot Kormelink T,Bezemer GF,Kerstjens HA,Postma DS,Garssen J,Kraneveld AD,Redegeld FA,Folkerts Gdoi
10.1164/rccm.201104-0761OCsubject
Has Abstractpub_date
2012-04-15 00:00:00pages
817-24issue
8eissn
1073-449Xissn
1535-4970pii
rccm.201104-0761OCjournal_volume
185pub_type
杂志文章abstract:RATIONALE:Epidemiological studies in older individuals have found an association between the use of angiotensin-converting enzyme (ACE) inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength, and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation (PR). ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
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abstract:RATIONALE:There is conflicting information about the development and resolution of airway inflammation and airway hyperresponsiveness (AHR) after repeated airway exposure to allergen in sensitized mice. METHODS:Sensitized BALB/c and C57BL/6 mice were exposed to repeated allergen challenge on 3, 7, or 11 occasions. Air...
journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.149.6.7516250
更新日期:1994-06-01 00:00:00
abstract::Previous studies reported linkage between maternally inherited atopy and the beta subunit of the high affinity IgE receptor (Fc epsilon RI-beta) located on chromosome 11q13. We have investigated 45 Italian families with atopic asthmatic children, for a total of 213 subjects, including 148 patients. Genotyping was carr...
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abstract:RATIONALE:The effect of indoor air pollutants on respiratory morbidity among patients with chronic obstructive pulmonary disease (COPD) in developed countries is uncertain. OBJECTIVES:The first longitudinal study to investigate the independent effects of indoor particulate matter (PM) and nitrogen dioxide (NO(2)) conc...
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.1.9703002
更新日期:1998-01-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2005-03-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:1995-09-01 00:00:00
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更新日期:2000-10-01 00:00:00
abstract:RATIONALE:The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma. OBJECTIVES:To analyze the interaction between lung function development and asthma from birth to 7 years of age. METHODS:The Copenhagen Prospe...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
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更新日期:2012-06-01 00:00:00
abstract:RATIONALE:Inhaled human insulin (INH; Exubera [human insulin (recombinant DNA origin) Inhalation Powder]) causes small changes in pulmonary function and increases in insulin antibodies compared with subcutaneous (SC) insulin. OBJECTIVES:To investigate the relationship between changes in pulmonary function and insulin ...
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abstract::In this case-control family study of sleep-disordered breathing (SDB), we describe the distributions of SDB and SDB risk factors in African-Americans and Caucasians. A total of 225 African-Americans and 622 Caucasians, ages 2 to 86 yr, recruited as members of families with an individual with known sleep apnea (85 inde...
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2000-03-01 00:00:00
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更新日期:2009-08-01 00:00:00
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更新日期:2001-05-01 00:00:00
abstract:RATIONALE:Low blood levels of 25-hydroxyvitamin D (25[OH]D) have been associated with a higher risk of respiratory infections in general populations and higher risk of exacerbations of lung disease in people with asthma. We hypothesized that low blood levels of 25(OH)D in patients with chronic obstructive pulmonary dis...
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pub_type: 杂志文章,随机对照试验
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更新日期:2012-02-01 00:00:00
abstract::Studies of the hemodynamic effects of nasal continuous positive airway pressure (n-CPAP) in normal subjects have had conflicting results. The largest study (n = 19) found no effect of up to 15 cm H2O on heart rate (HR), cardiac stroke volume (SV), or cardiac index. We hypothesized that n-CPAP, by increasing intrathora...
journal_title:American journal of respiratory and critical care medicine
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更新日期:1994-06-01 00:00:00
abstract::To investigate the utility of testing all tuberculosis patients for HIV infection in Los Angeles, we prospectively evaluated 183 hospitalized patients with acid-fast smear-positive tuberculosis who gave no history of HIV infection. HIV serologic testing was performed, and the presence of risk factors for HIV infection...
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abstract::Stenotrophomonas maltophilia is a gram-negative bacterium that has been cultured with increasing prevalence from the sputum of patients with cystic fibrosis (CF). We conducted a cohort study, using the Cystic Fibrosis Foundation Registry, to assess the effect of S. maltophilia on survival. We studied all patients in t...
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更新日期:2002-08-01 00:00:00
abstract::Because interleukin 8 (IL-8) is a potent neutrophil chemotactic and activating cytokine, we investigated IL-8 production in relation to neutrophil migration and elastase release in the human lung during unilateral community-acquired pneumonia (CAP). In 17 patients, the local response in the involved lung was compared ...
journal_title:American journal of respiratory and critical care medicine
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更新日期:1996-01-01 00:00:00
abstract::The clinical significance of minimal acute rejection (grade A1) in lung transplant recipients is unknown. We prospectively analyzed 1,159 transbronchial lung biopsies in 184 patients. Two hundred seventy-nine biopsies in 128 participants confirmed A1 histology at a mean postoperative day of 229 +/- 340. Sixty four of ...
journal_title:American journal of respiratory and critical care medicine
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更新日期:2004-11-01 00:00:00
abstract:RATIONALE:In San Francisco, 70% of the tuberculosis cases occur among foreign-born persons, mainly from China, the Philippines, and Mexico. We postulate that there are differences in the characteristics and risk factors for tuberculosis among these populations. OBJECTIVES:To determine the clinical, epidemiological and...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201212-2239OC
更新日期:2013-05-01 00:00:00