Increased Numbers of Hypodense Alveolar Macrophages in Patients with Bronchial Asthma

Chanez, Pascal; Bousquet, Jean; Couret, I.; Cornillac, Laure; Barnéon, G.; Vic, P.; Michel, François; Godard, P.

doi:10.1164/ajrccm/144.4.923

Cited by 54 publications

(33 citation statements)

References 11 publications

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“…The exact role for the alveolar macrophage in asthma seems to be complex, since some researchers postulate the involvement of macrophages and their products, whereas others do not. 1,5,11,[34][35][36] The inflammatory cells generate reactive oxygen species that might be crucial in airway inflammation. Although their production is increased in asthma and COPD, 11,37 the exact role of reactive oxygen species is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages

Broeke

Leusink-Muis

Hilberdink

et al. 2004

Laboratory Investigation

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Airway inflammation is a characteristic feature in airway diseases such as asthma and chronic obstructive pulmonary disease. Oxidative stress, caused by the excessive production of reactive oxygen species by inflammatory cells like macrophages, eosinophils and neutrophils, is thought to be important in the complex pathogenesis of such airway diseases. The calcium-sensing regulatory protein calmodulin (CaM) binds and regulates different target enzymes and proteins, including calcium channels. In the present study, we investigated whether CaM, via the modulation of calcium channel function, influences [Ca 2 þ ] i in pulmonary inflammatory cells, and consequently, modulates the production of reactive oxygen species by these cells. This was tested with a peptide termed calcium-like peptide 2 (CALP2), which was previously shown to regulate such channels. Specifically, radical production by purified broncho-alveolar lavage cells from guinea-pigs in response to CALP2 was measured. CALP2 was a strong activator of alveolar macrophages. In contrast, CALP2 was only a mild activator of neutrophils and did not induce radical production by eosinophils. The CALP2-induced radical production was mainly intracellular, and was completely blocked by the NADPH-oxidase inhibitor DPI, the superoxide inhibitor SOD and the CaM antagonist W7. Furthermore, the calcium channel blocker lanthanum partly inhibited the cellular activation by CALP2. We conclude that alveolar macrophages, but not neutrophils or eosinophils, can produce extremely high amounts of reactive oxygen species when stimulated via the calcium/CaM pathway. These results may contribute to new therapeutic strategies against oxidative stress in airway diseases.

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Section: Discussionmentioning

confidence: 99%

Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages

Broeke

Leusink-Muis

Hilberdink

et al. 2004

Laboratory Investigation

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“…Cells were differentiated using standard morphological criteria. In addition to total macrophage numbers, the number of cells which showed the morphological characteristics (enlargement, vesicles and cytoplasmic projections) of activated airway macrophages in human asthmatics [8,9] was determined. All differential cell counts were performed blind and in randomized order at the end of the study.…”

Section: Assessment Of Airway Inflammationmentioning

confidence: 99%

Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness

Underwood¹,

Foster²,

Raeburn³

et al. 1995

Eur Respir J

100

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The causative relationship between airway inflammation and hyperreactivity is unclear, since inflammatory changes have been examined at one or, at most, a few time-points after antigen challenge in both human asthma and animal models. We have made a detailed investigation of inflammatory and functional changes in the airways up to 8 days after antigen challenge in guinea-pigs. In particular, we examined the hypothesis that eosinophil-derived mediators contribute to tissue damage and the development of airway hyperresponsiveness.Following antigen challenge, the influx of inflammatory cells and mediator release in airway tissue and bronchoalveolar lavage fluid were correlated temporally with histopathological changes in airway tissue and airway responsiveness.Eosinophil influx was demonstrable at 4 h. Eosinophilia peaked after 24 h and persisted for at least 8 days. Parallel increases in the concentrations of major basic protein and eosinophil cationic protein in bronchoalveolar lavage fluid indicated that the eosinophils were activated. Eosinophilia was accompanied by subepithelial oedema and epithelial damage co-localized with major basic protein immunoreactivity. A transient neutrophilia (<48 h duration) and an increase in neutrophil elastase in bronchoalveolar lavage fluid peaked at 14 h. The proportion of airway macrophages with an activated morphology increased at 8 h and remained markedly elevated until 72 h. Airways were hyperresponsive to histamine at 4 h and for at least 8 days.The antigen-induced airway inflammation resemble in time-course and histopathology that seen in antigen-challenged asthmatics, and indicate that the eosinophil and its cytotoxic proteins may be major mediators of airway mucosal damage and airway hyperresponsiveness.

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“…It does not take into account the pulmonary function of the patients. Activity of asthma (stability versus instability) was established by a questionnaire as described previously [12]. Briefly, the stability of asthma was defined as the absence of any clinical events or β 2 -agonist inhalation during the last 2 weeks.…”

Section: Patientsmentioning

confidence: 99%

“…These two populations were classified according to activity of asthma, as described by TURNER WARWICK [11] and ourselves [12], rather than by severity as defined by the Aas' score. Phorbol myristate acetate (PMA) [13] was used for in vitro triggering of a protein kinase C activator which stimulates the NADPH oxidase system [14].…”

mentioning

confidence: 99%

Enhancement of reactive oxygen species formation in stable and unstable asthmatic patients

Vachier

Chanez²,

Doucen³

et al. 1994

Eur Respir J

107

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E En nh ha an nc ce em me en nt t o of f r re ea ac ct ti iv ve e o ox xy yg ge en n s sp pe ec ci ie es s f fo or rm ma at ti io on n i in n s st ta ab bl le e a an nd d u un ns st ta ab bl le e a as st th hm ma at ti ic c p pa at ti ie en nt ts s ABSTRACT: There is increasing evidence to suggest that human blood polymorphonuclear neutrophils (PMNs) and monocytes play an important role in the inflammatory processes of asthma. In asthmatic patients, PMNs and monocytes were shown to be activated more than in healthy subjects. We investigated the capacity of these two cell populations to generate reactive oxygen species (ROS) in stable and unstable asthmatic patients. The two populations of asthmatic patients were identified by asthma activity, as expressed by clinical events occurring within 2 weeks prior to the study. Oxygen species formation was analysed for isolated purified PMNs and monocytes (Mos) by chemiluminescence (CL) using lucigenin and luminol as luminescent probes. CL was determined on nonstimulated and on phorbol myristate acetate (PMA)-stimulated cells. The stimulatability coefficient (PMA-stimulated/nonstimulated cell ratio) of each cell population was then calculated.Resting PMNs and Mos generated significantly greater amounts of ROS in stable asthmatic patients, and much more in unstable asthmatic patients, as compared to healthy subjects, both in lucigenin and luminol enhanced CL. Non O 2 · -ROS production from PMA-stimulated PMNs and Mos was identical in unstable asthmatic patients and in healthy subjects, whereas a significant decrease was observed in stable asthmatic patients, as assessed by luminol enhanced CL. PMA-stimulated cells showed no difference in O 2 · -generation, as assessed by lucigenin enhanced CL. However, the stimulatability coefficient of all asthmatic patients was always significantly lower than that of healthy subjects.These results suggest that there are differences in priming and stimulation of Ros production from PMNs and Mos between stable and unstable asthmatic patients. Release of oxygen species from these cells may be implicated in the pathophysiology of unstable asthma.

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Increased Numbers of Hypodense Alveolar Macrophages in Patients with Bronchial Asthma

Cited by 54 publications

References 11 publications

Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages

Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages

Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness

Enhancement of reactive oxygen species formation in stable and unstable asthmatic patients

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