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E. coli lipopolysaccharide attenuates adenosine A1 receptor-mediated increase in plasma exudation from the hamster cheek pouch

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Abstract

Objective and design

To determine whether exposure to E. coli lipopolysaccharide (LPS) modulates adenosine A1 receptor-induced increase in plasma exudation from the intact hamster cheek pouch microcirculation.

Methods and results

Using intravital microscopy, we found that suffusion of R(−)-N 6-(2-phenylisopropyl)-adenosine (R(−)-PIA) (1.0 and 10.0 nM), a selective adenosine A1 receptor agonist, onto the intact cheek pouch elicited significant, concentration-dependent leaky site formation and increase in clearance of fluorescein thioisocyanate-dextran (mol mass, 70 kDa) from post-capillary venules (p < 0.05). These responses were significantly attenuated by pre-treatment of hamsters with LPS (p < 0.05). By contrast, LPS had no significant effects on CGS-21680-, a selective adenosine A2A receptor agonist, bradykinin- and substance P-induced increases in plasma exudation from the cheek pouch.

Conclusion

These data indicate that LPS attenuates adenosine A1 receptor-induced increase in plasma exudation in vivo in a specific fashion. We suggest that this phenomenon represents an endogenous anti-inflammatory cue to avoid excessive inflammation during Gram-negative bacterial infections.

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Acknowledgments

This study was supported in part by NIH Grants RO1 AG024026 and RO1 HL72343, and by VA Merit Review.

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Correspondence to Israel Rubinstein.

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Responsible Editor: Makoto Katori.

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Gao, Xp., Rubinstein, I. E. coli lipopolysaccharide attenuates adenosine A1 receptor-mediated increase in plasma exudation from the hamster cheek pouch. Inflamm. Res. 60, 195–201 (2011). https://doi.org/10.1007/s00011-010-0254-9

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  • DOI: https://doi.org/10.1007/s00011-010-0254-9

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