Unique Structural Features That Influence Neutrophil Emigration Into the Lung

Burns, Alan R.; Smith, C. Wayne; Walker, David C.

doi:10.1152/physrev.00023.2002

Cited by 260 publications

(280 citation statements)

References 260 publications

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“…35 However, such abundance of lung leukocytes may be also harmful during systemic inflammatory responses. Systemic release of CXCR2 agonists (TNF-a and IL1b) were directly related to an increased pulmonary neutrophilia and remote lung lesion during intestinal I/R injury.…”

Section: Discussionmentioning

confidence: 99%

Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure

Marques¹,

Amaral²,

Pires³

et al. 2012

Hepatology

278

259

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Acetaminophen (APAP) is a safe analgesic and antipyretic drug. However, APAP overdose leads to massive hepatocyte death. Cell death during APAP toxicity occurs by oncotic necrosis, in which the release of intracellular contents can elicit a reactive inflammatory response. We have previously demonstrated that an intravascular gradient of chemokines and mitochondria-derived formyl peptides collaborate to guide neutrophils to sites of liver necrosis by CXC chemokine receptor 2 (CXCR2) and formyl peptide receptor 1 (FPR1), respectively. Here, we investigated the role of CXCR2 chemokines and mitochondrial products during APAP-induced liver injury and in liver neutrophil influx and hepatotoxicity. During APAP overdose, neutrophils accumulated into the liver, and blockage of neutrophil infiltration by anti-granulocyte receptor 1 depletion or combined CXCR2-FPR1 antagonism significantly prevented hepatotoxicity. In agreement with our in vivo data, isolated human neutrophils were cytotoxic to HepG2 cells when cocultured, and the mechanism of neutrophil killing was dependent on direct contact with HepG2 cells and the CXCR2-FPR1-signaling pathway. Also, in mice and humans, serum levels of both mitochondrial DNA (mitDNA) and CXCR2 chemokines were higher during acute liver injury, suggesting that necrosis products may reach remote organs through the circulation, leading to a systemic inflammatory response. Accordingly, APAP-treated mice exhibited marked systemic inflammation and lung injury, which was prevented by CXCR2-FPR1 blockage and Toll-like receptor 9 (TLR9) absence (TLR9 2/2 mice). Conclusion: Chemokines and mitochondrial products (e.g., formyl peptides and mitDNA) collaborate in neutrophil-mediated injury and systemic inflammation during acute liver failure. Hepatocyte death is amplified by liver neutrophil infiltration, and the release of necrotic products into the circulation may trigger a systemic inflammatory response and remote lung injury.

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Section: Discussionmentioning

confidence: 99%

Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure

Marques¹,

Amaral²,

Pires³

et al. 2012

Hepatology

278

259

View full text Add to dashboard Cite

show abstract

“…49 By immunofluorescence, deposition of immunoglobulin may be granular (classical immune deposits as occur in certain renal diseases), or linear (as occurs in other renal diseases and Goodpasture's syndrome). Granular deposits are visible by immunofluorescence, electron microscopy, and sometimes even by light microscopy.…”

Section: Discussionmentioning

confidence: 99%

Alveolar Septal Deposition of Immunoglobulin and Complement Parallels Pulmonary Hemorrhage in a Guinea Pig Model of Severe Pulmonary Leptospirosis

Nally¹,

Chantranuwat²,

Wu³

et al. 2004

The American Journal of Pathology

177

183

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Human patients suffering from leptospirosis present with a diverse array of clinical manifestations, including the more severe and often fatal pulmonary form of the disease. The etiology of pulmonary hemorrhage is unclear. Isolates of Leptospira acquired from patients suffering from pulmonary hemorrhage were used to develop a guinea pig model of pulmonary hemorrhage. Gross findings post-infection confirmed extensive hemorrhage in the lungs and on peritoneal surfaces as the likely cause of death. Immunohistochemistry confirmed the presence of large numbers of leptospires in kidney, liver, intestinal tissues, and spleen, but few inflammatory cells were seen. In marked contrast, few leptospires were detected in infected hemorrhagic lung tissue. Blood chemistries and hematology did not reveal the etiology of the hemorrhage observed. There was no chemical or microscopic evidence for disseminated intravascular coagulation. To ascertain an immunopathologic role during disease, immunofluorescence was performed on infected lung tissues and confirmed the presence of IgM, IgG, IgA, and C3 along the alveolar basement membrane. This suggests that an autoimmune process may be the etiology of fatal pulmonary hemorrhage in lep-

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“…To reach the airway lumen, PMNs are required to travel through several distinct tissue compartments within the alveolar wall (8,9). PMNs must first escape the alveolar capillary, which involves the termination of their flow through the vessel followed by adherence to the lumen surface of the endothelium.…”

Section: Iseases Involving Bacterial-induced Lung Inflammationmentioning

confidence: 99%

Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3

Hurley

Siccardi

Mrsny

et al. 2004

The Journal of Immunology

160

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Lung inflammation resulting from bacterial infection of the respiratory mucosal surface in diseases such as cystic fibrosis and pneumonia contributes significantly to the pathology. A major consequence of the inflammatory response is the recruitment and accumulation of polymorphonuclear cells (PMNs) at the infection site. It is currently unclear what bacterial factors trigger this response and exactly how PMNs are directed across the epithelial barrier to the airway lumen. An in vitro model consisting of human PMNs and alveolar epithelial cells (A549) grown on inverted Transwell filters was used to determine whether bacteria are capable of inducing PMN migration across these epithelial barriers. A variety of lung pathogenic bacteria, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa are indeed capable of inducing PMN migration across A549 monolayers. This phenomenon is not mediated by LPS, but requires live bacteria infecting the apical surface. Bacterial interaction with the apical surface of A549 monolayers results in activation of epithelial responses, including the phosphorylation of ERK1/2 and secretion of the PMN chemokine IL-8. However, secretion of IL-8 in response to bacterial infection is neither necessary nor sufficient to mediate PMN transepithelial migration. Instead, PMN transepithelial migration is mediated by the eicosanoid hepoxilin A3, which is a PMN chemoattractant secreted by A549 cells in response to bacterial infection in a protein kinase C-dependent manner. These data suggest that bacterial-induced hepoxilin A3 secretion may represent a previously unrecognized inflammatory mechanism occurring within the lung epithelium during bacterial infections.

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Unique Structural Features That Influence Neutrophil Emigration Into the Lung

Cited by 260 publications

References 260 publications

Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure

Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure

Alveolar Septal Deposition of Immunoglobulin and Complement Parallels Pulmonary Hemorrhage in a Guinea Pig Model of Severe Pulmonary Leptospirosis

Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3

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