Deterioration of previous acute lung injury during neutropenia recovery*

Azoulay, Élie; Darmon, Michaël; Delclaux, Christophe; Fieux, Fabienne; Bornstain, Caroline; Moreau, Delphine; Attalah, Habiba; Gall, Jean-Roger Le; Schlemmer, Benoı̂t

doi:10.1097/00003246-200204000-00010

Cited by 127 publications

(103 citation statements)

References 35 publications

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“…Studies using various experimental models in animals have indicated that the severity of the ALI/ARDS course depends on the number of activated neutrophils infiltrating the lung (34). Although ARDS has been described in neutropenic patients (35), these findings do not exclude the central role of neutrophils in ARDS pathophysiology, because the recovery of patients from neutropenia was associated with deterioration of pulmonary function (36). Attenuation of neutrophil accumulation in the lungs, by using molecules inhibiting neutrophil adhesion, decreased the severity of lung injury (37).…”

Section: Discussionmentioning

confidence: 99%

C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

Kambas

Markiewski

Pneumatikos

et al. 2008

The Journal of Immunology

116

111

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Acute respiratory distress syndrome (ARDS) is characterized by the presence of fibrin-rich inflammatory exudates in the intra-alveolar spaces and the extensive migration of neutrophils into alveoli of the lungs. Tissue factor (TF)-dependent procoagulant properties of bronchoalveaolar lavage fluid (BALF) obtained from ARDS patients favor fibrin deposition, and are likely the result of cross-talk between inflammatory mediators and hemostatic mechanisms. However, the regulation of these interactions remains elusive. Prompted by previous findings suggesting that neutrophils, under certain inflammatory conditions, can express functional TF, we investigated the contribution of intra-alveolar neutrophils to the procoagulant properties of BALF from patients with ARDS. Our results confirm that the procoagulant properties of BALF from ARDS patients are the result of TF induction, and further indicate that BALF neutrophils are a main source of TF in intra-alveolar fluid. We also found that BALF neutrophils in these patients express significantly higher levels of TF than peripheral blood neutrophils. These results suggest that the alveolar microenvironment contributes to TF induction in ARDS. Additional experiments indicated that the ability of BALF to induce TF expression in neutrophils from healthy donors can be abolished by inhibiting C5a or TNF-α signaling, suggesting a primary role for these inflammatory mediators in the up-regulation of TF in alveolar neutrophils in ARDS. This cross-talk between inflammatory mediators and the induction of TF expression in intra-alveolar neutrophils may be a potential target for novel therapeutic strategies to limit ARDS-associated disturbances of coagulation.

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Section: Discussionmentioning

confidence: 99%

C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

Kambas

Markiewski

Pneumatikos

et al. 2008

The Journal of Immunology

116

111

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“…It is at this point that clinical and physiological manifestations of lung injury become first apparent. It is not surprising then, that the resolution of neutropenia is temporally associated with worsening lung function in neutropenic hosts [37]. Reports of ALI in neutropenic patients [38] merely emphasise the complexity and redundancy of disease mechanisms associated with lung injury.…”

Section: Biotraumamentioning

confidence: 99%

Ventilator-associated lung injury: a search for better therapeutic targets

Oeckler¹,

Hubmayr²

2007

European Respiratory Journal

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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a continuum of injury that may arise from a number of primary insults.Localised injury may progress due to trauma from mechanical ventilation, a finding that has led to intense debate in the clinical and experimental literature over optimal ventilator management. The implementation of low tidal volume strategies has led to an improvement in outcomes; however, mortality remains unacceptably high.In the current review, ventilator-associated lung injury is examined, as it relates to the pathophysiological changes beyond direct airway trauma in ALI and ARDS, and an attempt is made to provide a historical perspective to outline potential current and future pitfalls in the use of surrogate end-points and the discovery of potential biomarkers. The systemic responses that lead to multi-organ dysfunction, the leading causes of morbidity and mortality in ALI and ARDS, are caused by pro-inflammatory signalling cascades and the activation of such diverse mediators as reactive oxygen species, immune response elements, apoptotic constituents and coagulation proteins.These areas are examined, including key mediators, and possible future areas of interest are discussed, including the potential of an ''acute lung injury chip'' to integrate measured surrogate biomarkers with real-time clinical information to improve patient outcomes.

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“…Neutrophils appear to play a major role in the development of ALI. Although ALI can occur in the setting of neutropenia, in both experimental models and in patients, neutrophils have been demonstrated to potentiate the pulmonary inflammatory response associated with ALI (4,5). Given the important role that neutrophils play in ALI, central questions in the pathophysiology of this entity relate to mechanisms that contribute to the accumulation and activation of neutrophils in the lung.…”

Section: A Cute Lung Injury (Ali)mentioning

confidence: 99%

Involvement of Vitronectin in Lipopolysaccaride-Induced Acute Lung Injury

Tsuruta¹,

Park²,

Siegal

et al. 2007

The Journal of Immunology

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Vitronectin is present in large concentrations in serum and participates in regulation of humoral responses, including coagulation, fibrinolysis, and complement activation. Because alterations in coagulation and fibrinolysis are common in acute lung injury, we examined the role of vitronectin in LPS-induced pulmonary inflammation. Vitronectin concentrations were significantly increased in the lungs after LPS administration. Neutrophil numbers and proinflammatory cytokine levels, including IL-1β, MIP-2, KC, and IL-6, were significantly reduced in bronchoalveolar lavage fluid from vitronectin-deficient (vitronectin−/−) mice, as compared with vitronectin+/+ mice, after LPS exposure. Similarly, LPS induced increases in lung edema, myeloperoxidase-concentrations, and pulmonary proinflammatory cytokine concentrations were significantly lower in vitronectin−/− mice. Vitronectin−/− neutrophils demonstrated decreased KC-induced chemotaxis as compared with neutrophils from vitronectin+/+ mice, and incubation of vitronectin+/+ neutrophils with vitronectin was associated with increased chemotaxis. Vitronectin−/− neutrophils consistently produced more TNF-α, MIP-2, and IL-1β after LPS exposure than did vitronectin+/+ neutrophils and also showed greater degradation of IκB-α and increased LPS-induced nuclear accumulation of NF-κB compared with vitronectin+/+ neutrophils. These findings provide a novel vitronectin-dependent mechanism contributing to the development of acute lung injury.

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Deterioration of previous acute lung injury during neutropenia recovery*

Abstract: Patients with acute respiratory failure after prolonged neutropenia complicated by pneumonia are at increased risk for ARDS.

Cited by 127 publications

References 35 publications

C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

Ventilator-associated lung injury: a search for better therapeutic targets

Involvement of Vitronectin in Lipopolysaccaride-Induced Acute Lung Injury

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