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-1 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.
Inflammatory Chemokine Transport and Presentation in HEV : A Remote Control Mechanism for Monocyte Recruitment to Lymph Nodes in Inflamed Tissues
The data presented in this manuscript are original and have not been submitted for publication elsewhere. This study complies with National Institutes of Health (NIH) guidelines for the humane use of laboratory animals.
Abbreviations used in this paper: CFA, complete Freund's adjuvant; DC, dendritic cell; FRC, fibroblastic reticular cell; GFP, green fluorescent protein; HEV, high endothelial venule; hMCP-1ALEXA, Alexa-conjugated human MCP-1; KLH, keyhole limpet hemocyanin; MCP, monocyte chemotactic protein; PLN, peripheral LN; SLC, secondary lymphoid tissue chemokine.
Roger T. Palframan, Steffen Jung, Guiying Cheng, Wolfgang Weninger, Yi Luo, Martin Dorf, Dan R. Littman, Barrett J. Rollins, Hans Zweerink, Antal Rot, Ulrich H. von Andrian; Inflammatory Chemokine Transport and Presentation in HEV : A Remote Control Mechanism for Monocyte Recruitment to Lymph Nodes in Inflamed Tissues . J Exp Med 5 November 2001; 194 (9): 1361–1374. doi: https://doi.org/10.1084/jem.194.9.1361
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