Summary of vascular heterogeneity during homeostasis (A) and inflammation (B). Heterogeneity illustrated includes endothelial cell (EC) type, EC to pericyte (PC) ratios, basement membrane (BM) characteristics, and leukocyte adhesion molecule (LAM) and major histocompatibility complex (MHC) expression. Brain: Brain microvessels have continuous ECs with a high EC : PC ratio and thick basement membrane. During homeostasis, there is very low expression of LAMs and MHC molecules. E-selectin and P-selectin are upregulated during inflammation and contribute to leukocyte rolling. ICAM-1, ICAM-2, and VCAM-1 are upregulated and contribute to leukocyte arrest and crawling. PECAM-1 at cell junctions assists in leukocyte transmigration (TEM), and ICAM-1 and VCAM-1 are upregulated on PCs to guide leukocytes through the BM into the tissue. MHC Class I molecules can be upregulated, which signal to T cells. Lung: Lung ECs at the air-blood barrier are continuous. There is a relatively low EC:PC ratio and thin basement membrane. During homeostasis, there is low expression of LAMs and MHC molecules. E-selectin and P-selectin can be upregulated during inflammation but do not contribute leukocyte rolling. ICAM-1 is upregulated and contributes to leukocyte sequestration and arrest. PECAM-1 at cell junctions assists in leukocyte TEM, and ICAM-1 and VCAM-1 are upregulated on PCs. MHC Class II molecules can be upregulated, which signal to T cells. Kidney: Kidney glomerulus capillaries have fenestrated ECs with a moderate EC:PC ratio and thick basement membrane. During homeostasis, there is constitutive expression of ICAM-1 and ICAM-2 and low expression of MHC molecules. E-selectin can be upregulated during inflammation, but leukocyte rolling is debated in the glomerulus. Glomerular ECs rely on platelets for P-selectin. ICAM-1 and VCAM-1 are upregulated and contribute to leukocyte arrest and crawling. PECAM-1 at cell junctions assists in leukocyte TEM, and ICAM-1 is upregulated on PCs to guide leukocytes through the BM into the tissue. MHC Class I and II molecules can be upregulated. Liver: Liver sinusoidal capillaries have discontinuous ECs with a low EC:PC ratio and poorly defined basement membrane. During homeostasis, there is expression of ICAM-1, ICAM-2, VAP-1 and MHC molecules. E-selectin can be upregulated in a subset of ECs during inflammation but do not contribute leukocyte rolling. ICAM-1, VCAM-1, and VAP-1 are upregulated and contribute to leukocyte arrest and crawling. JAM-A at cell junctions assists in leukocyte TEM, and ICAM-1 and VCAM-1 are upregulated on PCs. MHC Class II molecules can be upregulated.