Imaging inflammatory leukocyte recruitment in kidney, lung and liver--challenges to the multi-step paradigm.

Intravital microscopy has been essential in establishing the multi-step paradigm that describes how leukocytes in the bloodstream interact with the blood vessel wall during the process of leukocyte recruitment. Much of this work has been performed in readily-visualized tissues such as the mesentery and the cremaster muscle, where leukocyte-endothelial cell interactions are restricted to postcapillary venules. However, the microvasculatures of the liver, lung and renal glomerulus differ markedly from these conventionally structured microvascular beds. Moreover, the liver, lung and kidney can be the target of life-threatening leukocyte-mediated inflammation. Therefore, a clear understanding of the mechanisms of leukocyte recruitment to these sites is critical. In this review, we examine the advances made in the understanding of leukocyte recruitment in the liver, lung and glomerulus, as determined using intravital microscopy. We describe how leukocyte recruitment to these sites occurs via mechanisms distinct from the conventional rolling/adhesion/transmigration paradigm, and in some cases involves adhesion molecules with minimal roles in conventional postcapillary venules. In addition, we describe how advanced forms of in vivo imaging in combination with novel approaches for labeling immune cell subsets is revealing new complexities in leukocyte function and immune cell interactions in these specialized microvascular beds.