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Articles

P-Selectin-Dependent Monocyte Recruitment Through Platelet Interaction in Intestinal Microvessels of LPS-Treated Mice

, , , , , , , , , , & show all
Pages 441-450 | Received 13 Apr 2007, Accepted 25 Sep 2007, Published online: 10 Jul 2009
 

Abstract

Background: Although platelets or monocytes are thought to be involved in intestinal inflammation, there has been no report on whether platelets can modulate monocyte recruitment in intestinal microvessels. The objective of this study was to determine whether blockade of platelet adhesion attenuates monocyte recruitment in inflamed murine intestinal microvessels. Methods: Monocytes and platelet-rich plasma were obtained from C57B6/J mice. Interaction of monocytes and platelets with intestinal microvessels was observed under an intravital microscope. Lipopolysaccharide (LPS) was administered intraperitoneally. The effects of anti-P-selectin or anti-platelets antibody treatments or phosphodiesterase (PDE) inhibitors (PDE-3 and PDE-2/4 inhibitor) treatments were also studied. Results: LPS-treatment increased the rolling and adhesion of both platelets and monocytes. Pretreatment with an anti-P-selectin antibody inhibited the increased platelet adhesion to venular walls and also attenuated the monocyte adhesion. A PDE-2/4 inhibitor (ibuzilast) also ameliorated both platelet and monocyte adhesion. A PDE-3 inhibitor (cilostazol) ameliorated only monocyte adhesion without directly affecting the adhesion of platelets to microvessels. Conclusions: We observed inhibition of platelets adhesion attenuated monocytes recruitment in intestinal microvessels. Attenuation of LPS induced monocyte adhesion by a specific PDE-3 inhibitor suggests that P-selectin on activated platelets may play an important role through monocyte and platelet interaction.

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