The role of selectins and integrins in adenovirus vector-induced neutrophil recruitment to the liver

Li, Yang; Muruve, Daniel A.; Collins, Robert G.; Lee, Samuel S.; Kubes, Paul

doi:10.1002/1521-4141(200212)32:12<3443::aid-immu3443>3.0.co;2-f

Cited by 36 publications

(28 citation statements)

References 40 publications

(58 reference statements)

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“…6,14 The expression of proinflammatory cytokines and chemokines is associated with leukocyte recruitment mediated by P-selectin, E-selectin and a 4 -integrin. 17 The prototypical activation of the innate immune response by Ad-vectors is associated with rapid clearance of the delivered vector dose (480%) in the first 24 h. 7 A thorough understanding of the mechanism by which Ad-vectors activate the innate arm of the immune system is required to overcome the last remaining hurdle limiting the efficiency and safety of adenovirus-mediated gene therapy in humans.…”

Section: Innate Immunity and The Early Host Response To Adenovirus Vementioning

confidence: 99%

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Molecular basis of the inflammatory response to adenovirus vectors

2003

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Section: Innate Immunity and The Early Host Response To Adenovirus Vementioning

confidence: 99%

“…36,37 The expression of leukocyte adhesion molecules facilitates leukocyte recruitment to adenovirus vector-transduced tissues. 17 Thus, adenovirus vectors induce a broad array of inflammatory genes in innate and noninnate cells that underlie the inflammatory response to these agents in vivo.…”

Section: Adenovirus Vectors and Inflammatory Gene Expressionmentioning

confidence: 99%

Molecular basis of the inflammatory response to adenovirus vectors

2003

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“…An alternative method to investigate cytokine expression is the use of adenoviral vectors for viralmediated gene transfer therapy. However, it has been established that the effectiveness may be limited by host immune defenses, demonstrated by rapid neutrophil-endothelial interactions induced by the adenoviral vectors (33). In our study, we chose a concentration of vector that is two-to fourfold lower than is usually reported.…”

Section: Discussionmentioning

confidence: 99%

Hepatic leukocyte recruitment in response to time-limited expression of TNF-α and IL-1β

Patrick

Rullo²,

Beaudin³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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The development of chronic liver diseases is mediated by sustained hepatic inflammation. Our objective was to characterize the molecular mechanisms responsible for the hepatic inflammatory response to time-limited TNF-α and IL-1β expression. C57Bl/6 mice were injected with 2 × 107plaque forming units intraperitoneally of an adenoviral vector containing TNF-α or IL-1β (AdTNF-α or AdIL-1β). A nonreplicating adenoviral vector served as control. Four days later, under ketamine and xylazine anesthesia, the liver microvasculature was examined by intravital microscopy. In the postsinusoidal venules, leukocyte rolling increased significantly in response to both AdTNF-α and AdIL-1β, compared with controls. This response was significantly reduced following injection of an anti-α4-integrin monoclonal antibody (MAb). Postsinusoidal rolling was further reduced to baseline following injection of an anti-P-selectin or anti-L-selectin MAb. Sinusoidal adhesion was greater in mice treated with AdIL-1β than with AdTNF-α. Blocking α4-integrin, P-selectin, or L-selectin had no significant effect on sinusoidal or postsinusoidal adhesion. In separate experiments, we administered AdTNF-α or AdIL-1β to mice deficient in ICAM-1. In ICAM-1−/− mice, postsinusoidal leukocyte rolling significantly increased following expression of IL-1β but not TNF-α. AdIL-1β- but not AdTNF-α-mediated sinusoidal adhesion was ICAM-1 dependent. AdTNF-α-induced sinusoidal adhesion was significantly reduced following 4 days of anti-MIP-2 MAb and anti-KC MAb. Prolonged expression of the cytokines TNF-α and IL-1β increases hepatic leukocyte-endothelial cell interactions. Interestingly, the mechanisms through which these cytokines bring about adhesion within the sinusoids differ; AdIL-1β sinusoidal adhesion uses an ICAM-1-dependent mechanism whereas AdTNF-α-mediated adhesion is ICAM-1 independent but CXC chemokine dependent.

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“…Indeed, administration of adenovirus vectors causes profound liver injury, but neutrophils were recruited almost exclusively to postsinusoidal venules, not to sinusoids (20). In this model of liver inflammation, neutrophil recruitment was amenable to antiadhesion therapy.…”

Section: Targeting Neutrophilsmentioning

confidence: 91%

II. Modulating leukocyte recruitment to splanchnic organs to reduce inflammation

Bonder

Kubes

2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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A hallmark feature of intestinal inflammation is the recruitment and extravasation of numerous cell types from the blood to the afflicted site. Much of what we know about the mechanisms of leukocyte recruitment to splanchnic organs comes from an extensive series of studies on neutrophils in the mesenteric microvasculature. In this themes article, we highlight the important findings from these experiments but also emphasize some of the limitations. In fact, there is a growing body of evidence that neutrophil recruitment may be quite different in the mesentery than in other splanchnic organs. For example, the molecular mechanisms underlying neutrophil recruitment into the liver are quite different than the mesentery and are dependent on the type of inflammatory disease. We also discuss the effect of modulating leukocyte recruitment to splanchnic organs in chronic inflammation and emphasize that the approaches that have been successful in acute inflammation may be less effective in such conditions as inflammatory bowel disease (IBD). One obvious reason for this observation is the growing body of evidence to suggest that the initiation and maintenance of IBD is, in part, due to dysregulated or inappropriately activated populations of infiltrating T lymphocyte subsets. Therefore, we also discuss some interesting new approaches to limiting lymphocyte recruitment into the inflamed intestine either by targeting T helper (Th)1 vs. Th2 lymphocytes or perhaps by allowing the recruitment of regulatory T cells. Inhibiting specific adhesion molecules or specific chemokine receptors may work in this regard.

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The role of selectins and integrins in adenovirus vector-induced neutrophil recruitment to the liver

Cited by 36 publications

References 40 publications

Molecular basis of the inflammatory response to adenovirus vectors

Molecular basis of the inflammatory response to adenovirus vectors

Hepatic leukocyte recruitment in response to time-limited expression of TNF-α and IL-1β

II. Modulating leukocyte recruitment to splanchnic organs to reduce inflammation

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