P-selectin-dependent monocyte recruitment through platelet interaction in intestinal microvessels of LPS-treated mice.
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.
Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Masaaki
M
Higashiyama
Ryota
R
Hokari
Hisayuki
H
Matsunaga
Koichi
K
Takebayashi
Chikako
C
Watanabe
Shunsuke
S
Komoto
Yoshikiyo
Y
Okada
Chie
C
Kurihara
Atsushi
A
Kawaguchi
Shigeaki
S
Nagao
Kazuro
K
Itoh
Soichiro
S
Miura
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007410:Intestinal Diseases / Q000139:chemically induced / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D019007:P-Selectin; D010727:Phosphoric Diester Hydrolases