The CC Chemokine Receptor Antagonist Met–RANTES Inhibits Eosinophil Effector Functions

Elsner, Jörn; Petering, Holger; Kimmig, Daniela; Wells, Timothy N. C.; Proudfoot, Amanda; Kapp, Alexander

doi:10.1159/000024164

Cited by 33 publications

(20 citation statements)

References 20 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of note, eotaxin-induced responses were only significantly inhibited when higher doses of Met-RANTES were given. These results are in agreement with our previous studies demonstrating a small, but significant inhibitory effect of high concentrations of Met-RANTES on murine CCR3 activation (5,29,30). Altogether, our results show that blockade of chemokine receptors with Met-RANTES is an effective strategy to block eosinophil recruitment.…”

Section: Discussionsupporting

confidence: 93%

Stem Cell Factor-Induced Leukotriene B4 Production Cooperates with Eotaxin to Mediate the Recruitment of Eosinophils During Allergic Pleurisy in Mice

Klein

Talvani

Silva

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The understanding of the mechanisms underlying eosinophil recruitment in vivo may aid in the development of novel strategies for the treatment of allergic disorders. In this study, we investigated the role of chemokines in the cascade of events leading to eosinophil recruitment in a stem cell factor (SCF)- and leukotriene B4 (LTB4)-dependent allergic pleurisy model in mice. The intrapleural administration of the eosinophil-active chemokines eotaxin, RANTES, and macrophage-inflammatory protein 1α (MIP-1α) induced a time- and dose-dependent eosinophil recruitment. Pretreatment with anti-eotaxin, but not anti-RANTES or anti-MIP-1α, blocked the recruitment of eosinophils following Ag challenge of sensitized animals, and significant eotaxin immunoreactivity was detected in the pleural cavity of these animals. Similarly, only the anti-eotaxin inhibited the eosinophil recruitment induced by injection of SCF in naive animals. However, blockade of SCF did not inhibit the release of eotaxin after Ag challenge of sensitized mice. Akin to its effects on SCF and in the allergic reaction, eotaxin-induced eosinophil recruitment was blocked by the LTB4 receptor antagonist CP105696. Nevertheless, SCF, but not eotaxin, appeared to regulate the endogenous release of LTB4 after Ag challenge. Finally, we show that low doses of eotaxin synergized with LTB4 to induce eosinophil recruitment in the pleural cavity. Overall, the present results show that eotaxin and SCF-induced LTB4 cooperate to induce eosinophil recruitment into sites of allergic inflammation. Cooperation between inflammatory mediators must be an important phenomenon in vivo, explaining both the ability of lower concentrations of mediators to induce a full-blown functional response and the effectiveness of different strategies at inhibiting these responses.

show abstract

Section: Discussionsupporting

confidence: 93%

Stem Cell Factor-Induced Leukotriene B4 Production Cooperates with Eotaxin to Mediate the Recruitment of Eosinophils During Allergic Pleurisy in Mice

Klein

Talvani

Silva

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…While chemokines are thought to primarily regulate the migration pattern of eosinophils, they have also been shown to promote eosinophil activation and function (Zimmermann et al, 2003). For example, RANTES and eotaxin-1 have been shown to promote cellular activation and modulate the respiratory burst (Elsner et al, 1997(Elsner et al, , 1999. Data presented eosinophil peroxidase release (A) and eosinophil-derived neurotoxin (EDN) plasma levels (B) from control subjects (n < 31), sickle cell anaemia patients (SCA, n < 27) and sickle cell anaemia patients on hydroxycarbamide therapy (SCAHC, n < 28).…”

Section: Discussionmentioning

confidence: 99%

Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients

et al. 2013

View full text Add to dashboard Cite

SummaryInflammation, leucocyte and red cell adhesion to the endothelium contribute to the pathogenesis of sickle cell anaemia. Neutrophils appear to be important for vaso-occlusion, however, eosinophils may also participate in this phenomenon. The role of eosinophils in the pathophysiology of sickle cell anaemia (SCA) and the effect of hydroxycarbamide (HC) therapy on the functional properties of these cells are not understood. Patients with SCA and those on HC therapy (SCAHC) were included in the study. SCAHC individuals presented significantly lower absolute numbers of eosinophils than SCA. Furthermore, SCAHC eosinophils demonstrated significantly lower adhesive properties, compared to SCA eosinophils. SCA and SCAHC eosinophils presented greater spontaneous migration when compared with control eosinophils. Baseline eosinophil peroxidase and reactive oxygen species release was higher for SCA individuals than for control individuals, as were plasma levels of eosinophil derived neurotoxin. SCAHC eosinophil degranulation was lower than that of SCA eosinophil degranulation. Eotaxin-1 and RANTES levels were higher in the plasma of SCA and SCAHC individuals, when compared with controls. These data suggest that eosinophils exist in an activated state in SCA and indicate that these cells play a role in the vaso-occlusive process. The exact mechanism by which HC may alter SCA eosinophil properties is not clear.

show abstract

“…Met-RANTES is a RANTES derivative which was shown to antagonize the effects of the chemokine in different experimental paradigms (Elsner et al, 1999;Proudfoot et al, 1999 (Fig. 6 A).…”

Section: Antagonism By Met-rantes Of the Hrantes Effects On [ 3 H]d-amentioning

confidence: 99%

RANTES Modulates the Release of Glutamate in Human Neocortex

Musante¹,

Longordo²,

Neri³

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

The CC Chemokine Receptor Antagonist Met–RANTES Inhibits Eosinophil Effector Functions

Cited by 33 publications

References 20 publications

Stem Cell Factor-Induced Leukotriene B4 Production Cooperates with Eotaxin to Mediate the Recruitment of Eosinophils During Allergic Pleurisy in Mice

Stem Cell Factor-Induced Leukotriene B4 Production Cooperates with Eotaxin to Mediate the Recruitment of Eosinophils During Allergic Pleurisy in Mice

Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients

RANTES Modulates the Release of Glutamate in Human Neocortex

Contact Info

Product

Resources

About