期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 194, 期 9, 页码 1361-1373出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.194.9.1361
关键词
homing; MCP-1; high endothelial venules; phagocytes; lymphatic system
资金
- NHLBI NIH HHS [HL62524, HL54936, HL56949] Funding Source: Medline
- NIAMS NIH HHS [AR42689] Funding Source: Medline
Interstitial fluid is constantly drained into lymph nodes (LNs) via afferent lymph vessels. This conduit enables monocyte-derived macrophages and dendritic cells to access LNs from peripheral tissues. We show that during inflammation 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 was over 100-fold upregulated and paralleled MCP-1 protein levels, whereas in 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 primarily derived from inflamed skin. In MCP-1(-/-) mice, intracutaneously injected MCP-I accumulated rapidly in the draining LNs where it enhanced monocyte recruitment. Intravital microscopy showed that skin-derived MCP-1 was transported via the lymph to the luminal surface of HEVs where it triggered integrin-dependent arrest of rolling monocytes. These findings demonstrate that 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.
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