Aerosolized Perfluorocarbon Suppresses Early Pulmonary Inflammatory Response in a Surfactant-Depleted Piglet Model

Chlamydophila pneumoniae alter the expression of Toll-like receptor (TLR) 4 in alveolar type II (ATII)-cells. Subsequently nuclear factor kappaB (NF-B) is activated and tumor necrosis factor-␣ (TNF-␣) and macrophage inflammatory protein 2 (MIP-2) are produced. Perfluorocarbons (PFC) are beneficial in animals with bacterial pneumonia and reduce production of TNF-␣. Using isolated ATII-cells, it was studied whether PFC prevent C. pneumoniae-induced TNF-␣ and MIP-2 release and what the underlying pathway is. PF5080 preincubation prevented C. pneumoniae-induced secretion of TNF-␣ (43 Ϯ 10 versus 661 Ϯ 41 pg/mL) and MIP-2 (573 Ϯ 41 versus 4786 Ϯ 502 pg/mL). The C. pneumoniae-induced 2.2-fold increase of TNF-␣ Receptor 1 expression was reduced by PF5080. C. pneumoniae reduced cytoplasmatic IB␣ (3.7 Ϯ 0.3 versus 14 Ϯ 1) and increased NF-B p65 (31 Ϯ 7.5 versus 3.6 Ϯ 1.1) compared with control. PF5080 prevented NF-B activation. TLR4 expression was 1.5-fold higher after C. pneumoniae incubation, but remained at control levels after PF5080 pretreatment. After 24 h of C. pneumoniae incubation, in 88 Ϯ 6% of cells bacteria were found in the perinuclear region and in 50% of these cells bacteria adhered to cellular surface. After PF5080 preincubation, C. pneumoniae were in 32 Ϯ 4% attached to and in 5 Ϯ 1% internalized in ATII-cells. Since PF5080 was found in ATII-cell membranes, PF5080 effect could be explained by an alteration of the cellular membrane, preventing activation of the inflammatory cascade. Chlamydophila pneumoniae are obligate intracellular Gram-negative bacteria that cause respiratory infections in pediatric populations and adults (1,2). Recent studies demonstrated the presence of C. pneumoniae in alveolar macrophages and ATII cells in patients with chronic obstructive pulmonary disease (COPD) (3). Whereas most respiratory infections with C. pneumoniae are self-limited (4), bacterial colonization can lead to infectious exacerbations and development of COPD (5). Because detection rate of C. pneumonia varies significantly (6), the clinical relevance of C. pneumoniae is still controversial.The effect of C. pneumoniae on isolated ATII-cells is well characterized. C. pneumoniae inhibit the surfactant metabolism of ATII-cells after internalization (7). Many of C. pneumoniae-induced effects are mediated by cytokines. C. pneumoniae act at the ATII cell membrane to induce the expression of TLR4 (8). TLR signaling is partly mediated by the transcription factor NF-B, which controls the expression of many genes involved in the inflammatory response (9). C. pneumoniae-induced activation of NF-B leads to a release of the chemokine MIP-2 and the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-␣) (8) and its receptor tumor necrosis factor receptor 1 (TNFR1). Together, they play an important role in bacterial infections and modulate the inflammatory process (10).PFC-administered as liquid (11), vapor (12), or gas (13) into the lung-represent an alternative approach to treat respiratory insufficiency. Intrat...

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“…PFC have been shown before to prevent the TNF-␣ production of either isolated cells or in animal models of lung injury (12,16).…”

Section: Discussionmentioning

confidence: 99%

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

et al. 2006

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“…For evaluation of pulmonary inflammatory response (16), we assessed gene expression of IL-1␤, IL-6, IL-8, IL-10, Endothelin-1, TGF-␤1, E-selectin, P-selectin and ICAM-1 in lung tissue of piglets receiving either HFOV or IMV. These cytokines have previously been shown to be regulated in this model of lung injury after 8 h of ventilation (4,16). To further elucidate the mechanism and to define the relative contribution of specific pulmonary cells to the inflammatory response, we determined mRNA expression of IL-8 in alveolar macrophages, bronchiolar epithelial cells, bronchiolar and vascular smooth muscle cells and cells of the alveolar septum.…”

Section: Abbreviationsmentioning

confidence: 99%

“…Anesthesia and operative preparation were performed as described previously (16,20,21). Briefly, animals were tracheotomized and intubated (4.0 mm endotracheal tube, Mallinckrodt, Hennef, Germany).…”

Section: Treatment Groupsmentioning

confidence: 99%

High Frequency Oscillatory Ventilation Suppresses Inflammatory Response in Lung Tissue and Microdissected Alveolar Macrophages in Surfactant Depleted Piglets

et al. 2004

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“…This system should prove useful in the testing of a variety of medica-tions potentially useful for pulmonary delivery. In preterm newborns, these include surfactant (24), perfluorocarbon (25), steroids (26), diuretics (27), nitrite (28), prostacyclin (29), prostaglandin E1 (30), and antibiotics, targeting a variety of disorders such as respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary hypertension and pneumonia.…”

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confidence: 99%

Making Babies Breathe Better—Hopeful Signals?: Commentary on articles by Minocchieri et al. on page 141, and Sood et al. on page 159

Bhandari

2008

Pediatr Res

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Aerosolized Perfluorocarbon Suppresses Early Pulmonary Inflammatory Response in a Surfactant-Depleted Piglet Model

Cited by 50 publications

References 27 publications

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

High Frequency Oscillatory Ventilation Suppresses Inflammatory Response in Lung Tissue and Microdissected Alveolar Macrophages in Surfactant Depleted Piglets

Making Babies Breathe Better—Hopeful Signals?: Commentary on articles by Minocchieri et al. on page 141, and Sood et al. on page 159

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