Rules of Recruitment for Th1 and Th2 Lymphocytes in Inflamed Liver: A Role for Alpha-4 Integrin and Vascular Adhesion Protein-1

Bonder, C. S., et al. (2005) Immunity, 23: 153–163

Speaker：林雅葶                           Date：2005/12/14, 15:10~16:00

Commentator：王志堯 老師                 Place：Room 601

Abstract

Leukocytes recruited into the inflamed sites during inflammation is called extravasation. Leukocytes roll along the microvasculature, chemokines on the endothelium activate leukocyte integrins, causing the leukocytes to adhere to the endothelium and subsequently emigrate from the vasculature. With the development of the intravital microscope to visualize the microvascular beds in vivo, it becomes clear that not all organs follow the same paradigm under all conditions¹. One unique feature of the liver is the presence of multiple compartments for leukocyte recruitment. Liver sinusoids and the postsinusoidal venules are tortuous, narrow conduits, cellular recruitment in here have been shown to be independent of many known adhesion molecules. This suggests that leukocyte recruitment in the liver is mediated by physical trapping rather than adhesive forces. In this study, the author report that ex vivo the polarized Th1 and Th2 lymphocytes use distinct recruitment mechanisms within Con A-mediated inflammation. Th1 cells use α4-integrin to traffic into postsinusoidal venules, whereas Th2 cells exclusively use VAP-1². Neither of these mechanisms involves P-selectin, despite the fact that P-selectin is significantly upregulated in the inflamed liver. Furthermore neutrophil rolling, but not adhesion, during Con A-mediated inflammation is mediated by VAP-1.

References

1.      Bonder, C.S., et al. (2004) Essential role for neutrophil recruitment to the liver in Concanavalin A-induced hepatitis. J. Immunol. 172: 45–53.

2.      Merinen, M., et al. (2005) Vascular adhesion protein-1 is involved in both acute and chronic inflammation in the mouse. Am. J. Pathol. 166: 793–800.