Leukocyte adhesion in the liver: Distinct adhesion paradigm from other organs

Abstract

Over the last 15 years, the “unifying paradigm of leukocyte recruitment” has been formulated and can be found in most Pathology and Immunology texts. The paradigm for leukocyte recruitment (summarized in Fig. 1 Fig. 1 A) involves selectins as essential (classical) mediators of the initial tethering and rolling of leukocytes in the microvasculature. Firm adhesion is then mediated by integrins, principally the β₂-integrins Mac-1 and LFA-1 for neutrophils and the α₄β₁ or α₄β₇ (often in some combination with β₂-integrins) for all other leukocytes. The integrins switch to their high avidity and/or affinity state following leukocyte activation by chemokines presented on the endothelium, allowing firm adhesion to occur. This then permits the leukocytes to emigrate out of the vasculature. Although this paradigm does hold true for a number of organ microvasculatures including mesentery, peritoneum, skeletal muscle, and skin, there appears to be a growing number of exceptions and none more obvious than the liver microvasculature (Fig. 1 Fig. 1 B). It has been shown that leukocyte recruitment in portal and central venules of the liver is very similar to that found in mesenteric and cremasteric venules (Fig. 1 Fig. 1 A). In contrast, as illustrated in Fig. 1 Fig. 1 B the distinctive structural and functional features of hepatic sinusoidal endothelium may contribute to the dramatic difference in the leukocyte trapping in the liver sinusoids. In this review we highlight the molecular mechanisms of leukocyte recruitment into the liver, particularly into the sinusoids, and compare and contrast these to the more classical pathways of leukocyte recruitment in both other vasculatures and other parts of the liver.