Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line

Varsano, Shabtai; Kaminsky, Marina; Kaiser, Meirav; Rashkovsky, Ludmila

doi:10.1136/thorax.55.5.364

Cited by 45 publications

(34 citation statements)

References 29 publications

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“…The formation of intrapulmonary ICs after allergen exposure may also activate complement cascade (13). According to this hypothesis, activated C5 components are primarily located at the epithelial side of the airway, and, in nonasthmatic individuals, the intrapulmonary activation of complement is well regulated (28). Consistent with this hypothesis, our data demonstrated that intrapulmonary C5 inhibition achieved an efficacy similar to that of systemic C5 inhibition at checkpoint 3 ( Figure 8) and at checkpoint 2 (unpublished observations).…”

Section: Figuresupporting

confidence: 78%

Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response

Peng

Hao²,

Madri³

et al. 2005

J. Clin. Invest.

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The role of complement component C5 in asthma remains controversial. Here we examined the contribution of C5 at 3 critical checkpoints during the course of disease. Using an mAb specific for C5, we were able to evaluate the contribution of C5 during (a) the initiation of airway inflammation, (b) the maintenance of airway hyperresponsiveness (AHR), and (c) sustainment of an ongoing airway response to allergen provocation. Our results indicate that C5 is probably activated intrapulmonarily after infections or exposures to allergen and C5 inhibition has profound effects at all 3 critical checkpoints. In contrast to an earlier report, C5-deficient mice with established airway inflammation did not have elevated AHR to nonspecific stimuli. In the presence of airway inflammation, C5a serves as a direct link between the innate immune system and the development of AHR by engaging directly with its receptors expressed in airways. Through their powerful chemotactic and cell activation properties, both C5a and C5b-9 regulate the downstream inflammatory cascade, which results in a massive migration of inflammatory cells into the bronchial airway lumen and triggers the release of multiple harmful inflammatory mediators. This study suggests that targeting C5 is a potential clinical approach for treating patients with asthma.

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Section: Figuresupporting

confidence: 78%

Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response

Peng

Hao²,

Madri³

et al. 2005

J. Clin. Invest.

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“…These events result in inhibition oxidative burst and bacterial clearance by PMNs due to defective assembly of NADPH oxidase [21]. The ability of lung cells to synthesize C3 and C5 as well as other complement proteins locally can further contribute to the pathogenesis of lung disease [22][23][24].…”

Section: Immune Complex Injury Modelmentioning

confidence: 99%

Complement in lung disease

2006

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Complement proteins play an integral role in both innate and adaptive immune responses of the host. Complement activation leads to the formation of bioactive molecules including the anaphylatoxins, C3a and C5a, and the lytic membrane attack complex (C5b-9). These molecules trigger a series of events that culminate in the recruitment of phagocytic cells, release of cytokines/chemokines and reactive oxygen species, enhanced expression of adhesion molecules and apoptosis at the site of inflammation. Several animal models provide evidence that this series of events forms the basis for the pathophysiology found in many lung diseases, such as asthma and acute respiratory distress syndrome. Clinical data further confirm these findings. This review briefly discusses recent data from such studies.

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“…Although C6 production by pulmonary epithelial cells has not been assessed, bronchial epithelial and type II pneumocyte cell lines have been found to produce C3 and C5 (45)(46)(47). Complement synthesis by these cells is upregulated in response to IL-1and TNF-␣.…”

Section: Figurementioning

confidence: 99%

“…Moreover, by 7 days after transplantation, macrophages constituted a large percentage of the infiltrates in the peribronchial, perivascular, and interstitial spaces of lung allografts. In addition, alveolar epithelial cells also produce early components of complement (45)(46)(47). Therefore, we investigated whether lung allografts can be a source of C6.…”

Section: Local C6 Production By Lung Allograftsmentioning

confidence: 99%

Membrane Attack Complex Contributes to Destruction of Vascular Integrity in Acute Lung Allograft Rejection

Nakashima

Qian

Rahimi

et al. 2002

The Journal of Immunology

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The lung is known to be particularly susceptible to complement-mediated injury. Both C5a and the membrane attack complex (MAC), which is formed by the terminal components of complement (C5b-C9), can cause acute pulmonary distress in nontransplanted lungs. We used C6-deficient rats to investigate whether MAC causes injury to lung allografts. PVG.R8 lungs were transplanted orthotopically to MHC class I-incompatible PVG.1U recipients. Allografts from C6-sufficient (C6+) donors to C6+ recipients were rejected with an intense vascular infiltration and diffuse alveolar hemorrhage 7 days after transplantation (n = 5). Ab and complement (C3d) deposition was accompanied by extensive vascular endothelial injury and intravascular release of von Willebrand factor. In contrast, lung allografts from C6-deficient (C6−) donors to C6− recipients survived 13–17 days (n = 5). In the absence of C6, perivascular mononuclear infiltrates of ED1+ macrophages and CD8+ T lymphocytes were present 7 days after transplantation, but vascular endothelial cells were quiescent, with minimal von Willebrand factor release and no evidence of alveolar hemorrhage or edema. Lung allografts were performed from C6− donors to C6+ recipients (n = 5) and from C6+ donors to C6− recipients (n = 5) to separate the effects of systemic and local C6 production. Lungs transplanted from C6+ donors to C6− recipients had increased alveolar macrophages and capillary injury. C6 production by lung allografts was demonstrated at the mRNA and protein levels. These results demonstrate that MAC causes vascular injury in lung allografts and that the location of injury is dependent on the source of C6.

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Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line

Cited by 45 publications

References 29 publications

Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response

Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response

Complement in lung disease

Membrane Attack Complex Contributes to Destruction of Vascular Integrity in Acute Lung Allograft Rejection

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