Leukocyte‐endothelial cell adhesion: avenues for therapeutic intervention

Panés, Julián; Perry, Michael A.; Granger, D. Neil

doi:10.1038/sj.bjp.0702328

Cited by 245 publications

(180 citation statements)

References 96 publications

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“…These findings are in accordance with a previous study in which the percentages of basophils and eosinophils, leukocytes and monocytes were reduced by glucocorticoids in stressed animals (O'Connor et al, 2000). This inhibition is mediated at the level of cytokine gene transcription, and by inhibition of the production of arachidonic acid-derived proinflammatory substances (Panes et al, 2009). However, rise of blood neutrophil concentrations in the presence of glucocorticoids because of impaired endothelial cell adhesion, and consequently impaired diapedesis and migration to inflammatory sites (Doukas et al, 1988).…”

Section: Discussionsupporting

confidence: 93%

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Yong

et al. 2014

Animal

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Global warming is a challenge to animal health, because of increased heat stress, with subsequent induction of immunosuppression and increased susceptibility to disease. Toll-like receptors (TLR) are pattern recognition receptors that act as sentinels of pathogen invasion and tissue damage. Ligation of TLRs results in a signaling cascade and production of inflammatory cytokines, which eradicate pathogens and maintain the health of the host. We hypothesized that the TLR signaling pathway plays a role in immunosuppression in heat-stressed pigs. We explored the changes in the expression of TLR2, TLR4 and the concentration of acute inflammatory cytokines, such as IL-2, IL-8, IL-12 and IFN-γ in Bama miniature pigs subjected to 21 consecutive days of heat stress, both in vitro and in vivo models. The results showed that heat stress induced the upregulation of cortisol in the plasma of pigs (P < 0.05); TLR4 mRNA was elevated, but IL-2 was reduced in peripheral blood mononuclear cells (PBMC, P < 0.05). The white blood cell count and the percentage of granulocytes (eosinophilic + basophilic) decreased significantly in heat-stressed pigs (P < 0.05). In the in vitro model (PBMC heat shocked for 1 h followed by a 9 h recovery period), TLR2 and TLR4 mRNA expression also increased, as did the concentration of IL-12 in supernatants. However, IFN-γ was significantly reduced in PBMC culture supernatants (P < 0.05). We concluded that a consecutive heat stress period elevated the expression of TLR2 and TLR4 in PBMC and increased the plasma levels of inflammatory cytokines. These data indicate that TLR activation and dysregulation of cytokine expression in response to prolonged heat stress may be associated with immunosuppression and increased susceptibility to antigenic challenge in Bama miniature pigs.

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Section: Discussionsupporting

confidence: 93%

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Yong

et al. 2014

Animal

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“…In 1989, Osborn et al (24) reported that IL-1 was able to augment the adhesiveness of the vascular endothelium. This cytokine, along with others such as TNF-␣, up-regulate ICAM-1 and E-selectin expression (25). Our results, from experiments conducted in normal skin, indicate that IL-1␤ induced significant neutrophil accumulation at 0.3 pmol/site, but this was not observed with higher doses, with similar results in wild-type and knockout mice.…”

Section: Discussionsupporting

confidence: 69%

Neurokinin-1 Receptor Agonists Are Involved in Mediating Neutrophil Accumulation in the Inflamed, But Not Normal, Cutaneous Microvasculature: An In Vivo Study Using Neurokinin-1 Receptor Knockout Mice

Cao¹,

Pintér²,

Al-Rashed³

et al. 2000

The Journal of Immunology

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We have used tachykinin neurokinin-1 receptor (NK1 receptor) knockout mice to learn of the link between NK1 receptors and neutrophil accumulation in normal naive skin, as compared with inflamed skin. Intradermal substance P (300 pmol) induced edema formation in wild-type mice, but not in NK1 knockout mice, as expected. However, in contrast to IL-1β (0.3 pmol), substance P did not induce neutrophil accumulation in wild-type mice. IL-1β-induced neutrophil accumulation was similar in wild-type and knockout mice, but a significant (p < 0.05) contributory effect of added NK1 agonists, which by themselves have no effect on neutrophil accumulation in normal skin, was observed. The results support the concept that NK1 agonists such as substance P cannot act on their own to mediate neutrophil accumulation in naive skin and provide direct evidence that in inflamed skin, under certain circumstances, the NK1 receptor can play a pivotal role in modulating neutrophil accumulation during the ongoing inflammatory process. We investigated responses to two inflammatory stimuli (carrageenin and zymosan). Neutrophil accumulation was significantly attenuated (p < 0.001) in carrageenin- but not zymosan-induced inflammation in NK1 knockout mice. The carrageenin (500 μg)-induced response was inhibited (p < 0.05) by a NK1 receptor antagonist, SR140333 (480 nmol/kg i.v. at −5 min), in the wild-type group. The bradykinin B1 and B2 receptor antagonists (desArg9[Leu8]bradykinin and HOE 140) each reduced neutrophil accumulation to carrageenin in wild-type animals (p < 0.05), but did not cause further reduction of the suppressed response of knockout mice. The results provide evidence that kinin receptors participate in NK1 receptor-dependent neutrophil accumulation in inflamed mouse skin.

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“…IL-1␤ together with TNF-␣ are potent inducers of ICAM-1 expression which has previously been shown to be a requirement for neutrophil recruitment after airway instillation of LPS (24,25,35). Therefore, we postulated that the beneficial effect of ebselen might occur through the ability of this agent to prevent lung ICAM-1 expression.…”

Section: Effect Of Ebselen On Lung Icam-1 Expressionmentioning

confidence: 98%

Differential Effects of Ebselen on Neutrophil Recruitment, Chemokine, and Inflammatory Mediator Expression in a Rat Model of Lipopolysaccharide-Induced Pulmonary Inflammation

Haddad

McCluskie

Birrell

et al. 2002

The Journal of Immunology

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We postulated that the seleno-organic compound ebselen would attenuate neutrophil recruitment and activation after aerosolized challenge with endotoxin (LPS) through its effect as an antioxidant and inhibitor of gene activation. Rats were given ebselen (1–100 mg/kg i.p.) followed by aerosolized LPS exposure (0.3 mg/ml for 30 min). Airway inflammatory indices were measured 4 h postchallenge. Bronchoalveolar lavage (BAL) fluid cellularity and myeloperoxidase activity were used as a measure of neutrophil recruitment and activation. RT-PCR analysis was performed in lung tissue to assess gene expression of TNF-α, cytokine-induced neutrophil chemoattractant-1 (CINC-1), macrophage-inflammatory protein-2 (MIP-2), ICAM-1, IL-10, and inducible NO synthase. Protein levels in lung and BAL were also determined by ELISA. Ebselen pretreatment inhibited neutrophil influx and activation as assessed by BAL fluid cellularity and myeloperoxidase activity in cell-free BAL and BAL cell homogenates. This protective effect was accompanied by a significant reduction in lung and BAL fluid TNF-α and IL-1β protein and/or mRNA levels. Ebselen pretreatment also prevented lung ICAM-1 mRNA up-regulation in response to airway challenge with LPS. This was not a global effect of ebselen on LPS-induced gene expression, because the rise in lung and BAL CINC-1 and MIP-2 protein levels were unaffected as were lung mRNA expressions for CINC-1, MIP-2, IL-10, and inducible NO synthase. These data suggest that the anti-inflammatory properties of ebselen are achieved through an inhibition of lung ICAM-1 expression possibly through an inhibition of TNF-α and IL-1β, which are potent neutrophil recruiting mediators and effective inducers of ICAM-1 expression.

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Leukocyte‐endothelial cell adhesion: avenues for therapeutic intervention

Abstract: British Journal of Pharmacology (1999) 126, 537–550; doi:

Cited by 245 publications

References 96 publications

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Neurokinin-1 Receptor Agonists Are Involved in Mediating Neutrophil Accumulation in the Inflamed, But Not Normal, Cutaneous Microvasculature: An In Vivo Study Using Neurokinin-1 Receptor Knockout Mice

Differential Effects of Ebselen on Neutrophil Recruitment, Chemokine, and Inflammatory Mediator Expression in a Rat Model of Lipopolysaccharide-Induced Pulmonary Inflammation

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