Cytokines. 2. Cytokines and lung inflammation: mechanisms of neutrophil recruitment to the lung.

Strieter, Robert M.; Lukacs, Nicholas W.; Standiford, T. J.; Kunkel, Steven L.

doi:10.1136/thx.48.7.765

Cited by 85 publications

(54 citation statements)

References 48 publications

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“…Activated macrophages and nonmyeloid lung effector cells each promote the migration of neutrophils based on the production of various inflammatory mediators (38,39). Our analysis of cytokine levels in BALFs of IC-challenged mice revealed normal (CXCL1) to moderately decreased (CCL3 and TNF-a) cytokine levels in the absence of either Ga i2 or Ga i3 , and of reduced CXCL2 in the absence of Ga i2 (Fig.…”

Section: Discussionmentioning

confidence: 98%

Gαi2 Is the Essential Gαi Protein in Immune Complex–Induced Lung Disease

Wiege

Ali

Gewecke

et al. 2013

The Journal of Immunology

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Heterotrimeric G proteins of the Gαi family have been implicated in signaling pathways regulating cell migration in immune diseases. The Gαi-protein–coupled C5a receptor is a critical regulator of IgG FcR function in experimental models of immune complex (IC)–induced inflammation. By using mice deficient for Gαi2 or Gαi3, we show that Gαi2 is necessary for neutrophil influx in skin and lung Arthus reactions and agonist-induced neutrophilia in the peritoneum, whereas Gαi3 plays a less critical but variable role. Detailed analyses of the pulmonary IC-induced inflammatory response revealed several shared functions of Gαi2 and Gαi3, including mediating C5a anaphylatoxin receptor–induced activation of macrophages, involvement in alveolar production of chemokines, transition of neutrophils from bone marrow into blood, and modulation of CD11b and CD62L expression that account for neutrophil adhesion to endothelial cells. Interestingly, C5a-stimulated endothelial polymorphonuclear neutrophil transmigration, but not chemotaxis, is enhanced versus reduced in the absence of neutrophil Gαi3 or Gαi2, respectively, and knockdown of endothelial Gαi2 caused decreased transmigration of wild-type neutrophils. These data demonstrate that Gαi2 and Gαi3 contribute to inflammation by redundant, overlapping, and Gαi-isoform–specific mechanisms, with Gαi2 exhibiting unique functions in both neutrophils and endothelial cells that appear essential for polymorphonuclear neutrophil recruitment in IC disease.

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Section: Discussionmentioning

confidence: 98%

Gαi2 Is the Essential Gαi Protein in Immune Complex–Induced Lung Disease

Wiege

Ali

Gewecke

et al. 2013

The Journal of Immunology

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“…The process of neutrophil infiltration involves a series of steps: expression of endothelial cell adhesion molecules, neutrophil-endothelial cell adhesion, neutrophil activation and expression of neutrophilderived adhesion molecules, neutrophil diapedesis and migration beyond the vascular barrier along a neutrophil-specific chemotactic gradient. Both TNF-α and IL-1 strongly upregulate or induce the adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin) on the vascular endothelium [119]. Other effects by which these cytokines can facilitate neutrophil sequestration in the lungs include adhesion molecule expression on neutrophils and on the respiratory epithelium [119,126] and induction of chemoattractant cytokines, such as IL-8, by endothelial, lung epithelial or inflammatory cells [70].…”

Section: Cytokine Effects On the Respiratory Tractmentioning

confidence: 99%

“…Both TNF-α and IL-1 strongly upregulate or induce the adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin) on the vascular endothelium [119]. Other effects by which these cytokines can facilitate neutrophil sequestration in the lungs include adhesion molecule expression on neutrophils and on the respiratory epithelium [119,126] and induction of chemoattractant cytokines, such as IL-8, by endothelial, lung epithelial or inflammatory cells [70]. TNF-α and IL-1 were initially reported to have direct chemotactic activities.…”

Section: Cytokine Effects On the Respiratory Tractmentioning

confidence: 99%

Proinflammatory cytokines and viral respiratory disease in pigs

2000

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-Swine influenza virus (SIV), porcine respiratory coronavirus (PRCV) and porcine reproductive and respiratory syndrome virus (PRRSV) are enzootic viruses causing pulmonary infections in pigs. The first part of this review concentrates on known clinical and pathogenetic features of these infections. SIV is a primary respiratory pathogen; PRCV and PRRSV, on the contrary, tend to cause subclinical infections if uncomplicated but they appear to be important contributors to multifactorial respiratory diseases. The exact mechanisms whereby these viruses cause symptoms and pathology, however, remain unresolved. Classical studies of pathogenesis have revealed different lung cell tropisms and replication kinetics for each of these viruses and they suggest the involvement of different lung inflammatory responses or mediators. The proinflammatory cytokines interferon-α (IFN-α), tumour necrosis factor-α (TNF-α) and interleukin-1 (IL-1) have been shown to play key roles in several respiratory disease conditions. The biological effects of these cytokines and their involvement in human viral respiratory disease are discussed in the second part of this review. The third part summarises studies that were recently undertaken in the authors' laboratory to investigate the relationship between respiratory disease in pigs and bioactive lung lavage levels of IFN-α, TNF-α and IL-1 during single and combined infections with the above viruses. In single SIV infections, typical signs of swine "flu" were tightly correlated with an excessive and coordinate production of the 3 cytokines examined. PRCV or PRRSV infections, in contrast, were subclinical and did not induce production of all 3 cytokines. Combined infections with these 2 subclinical respiratory viruses failed to potentiate disease or cytokine production. After combined inoculation with PRCV followed by bacterial lipopolysaccharide, both clinical respiratory disease and TNF-α/IL-1 production were markedly more severe than those associated with the respective single inoculations. Taken together, these data are the first to demonstrate that proinflammatory cytokines can be important mediators of viral respiratory diseases in pigs. respiratory coronavirus, PRCV), et le virus du syndrome dysgénésique et respiratoire porcin (porcine reproductive and respiratory syndrome virus, PRRSV) sont des virus enzootiques provoquant des infections pulmonaires chez le porc. Les caractéristiques cliniques et pathogénétiques de ces infections sont données dans la première partie de cette revue. Le SIV est un agent pathogène respiratoire primaire ; les PRCV et PRRSV, en revanche, ne causent que des infections subcliniques en l'absence de complications, mais ils contribuent de manière importante aux maladies respiratoires multifactorielles. Cependant, les mécanismes précis par lesquels ces virus provoquent des symptômes et une pathologie demeurent inconnus. Les études classiques de pathogenèse ont révélé un tropisme pour les cellules pulmonaires et des cinétiques de réplication différents pour...

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“…Neutrophil adherence and degranulation are key steps in initiation of this process, which is the subject of recent reviews [58,59]. The neutrophil activation process consists of polarisation and locomotion, adherence, phagocytosis and degranulation.…”

Section: Effect Of Anaesthetic Agents On Neutrophil Functionmentioning

confidence: 99%

Immunomodulation: an important concept in modern anaesthesia

McBride¹,

1996

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Summary ihirgrd anions such as heparin. Neutrophil actirity is generally depressed by intravenous unaesthetic induction agents, hut is enhanced by 0pioid.y. Natural killer cell activity, which is invohed in immunity against tuniour cells and iGrully infbcted cells is transientlr depressed by volatile anaesthetic agents and opioids. In contrast catecholamines enhance natural killer cell activity. Whereas drcrease in inimunoglobulin levels occur peri-operaticely, this is not thought to be us a result of drugs at clinicully used concentratiows but rather due to haemodilution. Key wordsIniniune responsc .The possible effects of anaesthesia on the immune system have been discussed from as early as 1916 [I]. This review discusses how drugs commonly used in anaesthesia and intensive care may modulate immunological parameters and looks beyond currently published work to those areas likely to be of clinical importance in the near future. Excellent guidance on basic imniunopharmacology may be found in several specialist tests, for instance Dale, Foreman and Young, Trsthook of Init~iirnopharnir~cology (Blackwell Scientific Publications) [2]. Basic structure of the immune system Innutr und adaptii~e initnunit! (Fig. I )Any immune response involves recognition of an infectious agent or other foreign material and the resulting reaction against it to remove it. The natural or innate response is rapid. non-specific for the antigen and does not improve upon repeated exposure. In contrast, the adaptive response is highly specific for a particular antigen and improves upon successive exposure to that antigen, constituting a memory mechanism which protects against future encounters with the antigen. Innate immune responses are mediated by natural killer (NK) cells and phagocytic cells such as monocytes, macrophages and polymorphonuclear neutrophils which use primitive nonspecific recognition systems to bind micro-organisms, then neutralise and destroy them. Lymphocytes are central to all adaptive immune responses, specifically recognising the antigen and initiating the response to it. B-lymphocytes release antibody which specifically recognises and binds to extracellular pathogens and their products (humoral immune response). T-lymphocytes are composed of subsets termed T-helper 1 ( T H~) , The effects of opioids on NK cell activity is controversial, and depends on the experimental system studied. It has been postulated that natural killer cells have opioid receptors and it is thought that through this mechanism 8-endorphin in vitro can augment the cytolytic activity of natural killer cells-an effect which can be blocked by naloxone [5, 61. In a rat model, stress-induced endorphins were found to have an inhibitory effect on natural killer cell activity, an effect which could be mimicked by high-dose morphine and blocked by naloxone [7]. In a preliminary report, anaesthesia in patients using a high-dose fentanyl technique led to a depression in natural killer activity lasting for 3 days. This effect could be reversed in vitro by add...

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Cytokines. 2. Cytokines and lung inflammation: mechanisms of neutrophil recruitment to the lung.

Cited by 85 publications

References 48 publications

Gαi2 Is the Essential Gαi Protein in Immune Complex–Induced Lung Disease

Gαi2 Is the Essential Gαi Protein in Immune Complex–Induced Lung Disease

Proinflammatory cytokines and viral respiratory disease in pigs

Immunomodulation: an important concept in modern anaesthesia

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