Inflammatory chemokine transport and presentation in HEV: A remote controlmechanism for monocyte recruitment to lymph nodes in inflamed tissues

Interstitial fluid is constantly drained into lymph nodes (LNs) via afferen t lymph vessels. This conduit enables monocyte-derived macrophages and dend ritic cells to access LNs from peripheral tissues. We show that during infl ammation in the skin, a second recruitment pathway is evoked that recruits large numbers of blood-borne monocytes to LNs via high endothelial venules (HEVs). Inhibition of monocyte chemoattractant protein (MCP)-1 blocked this inflammation-induced monocyte homing to LNs. MCP-1 mRNA in inflamed skin w as over 100-fold upregulated and paralleled MCP-1 protein levels, whereas i n draining LNs MCP-1 mRNA induction was much weaker and occurred only after a pronounced rise in MCP-1 protein. Thus, MCP-1 in draining LNs was primar ily derived from inflamed skin. In MCP-1(-/-) mice, intracutaneously inject ed MCP-I accumulated rapidly in the draining LNs where it enhanced monocyte recruitment. Intravital microscopy showed that skin-derived MCP-1 was tran sported via the lymph to the luminal surface of HEVs where it triggered int egrin-dependent arrest of rolling monocytes. These findings demonstrate tha t inflamed peripheral tissues project their local chemokine profile to HEVs in draining LNs and thereby exert "remote control" over the composition of leukocyte populations that home to these organs from the blood.