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PMID: 11696600 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues.

The Journal of experimental medicine ·Vol. 194 ·No. 9 ·2001-11-05 ·Pages 1361-73

Palframan RT, Jung S, Cheng G, Weninger W, Luo Y, Dorf M, Littman DR, Rollins BJ, Zweerink H, Rot A, von Andrian UH

Abstract

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.

MeSH Terms
Adoptive Transfer Animals Antigen Presentation/immunology Antigens/immunology Biological Transport Chemokine CCL2/administration & dosage,immunology,metabolism Chemotaxis/immunology Endothelium, Lymphatic/immunology Female Freund's Adjuvant Hemocyanins/immunology Leukocytes, Mononuclear/immunology Lymph Nodes/immunology Macrophages/immunology Male Mice Mice, Inbred C57BL Mice, Knockout Monocytes/immunology Phagocytosis/immunology Skin/immunology
Chemicals
Antigens Chemokine CCL2 Freund's Adjuvant Hemocyanins keyhole-limpet hemocyanin
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Palframan R T
Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
Jung S
Cheng G
Weninger W
Luo Y
Dorf M
Littman D R
Rollins B J
Zweerink H
Rot A
von Andrian U H
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.194.9.1361
Published
2001-11-05
Pages
1361-73
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195988
Subset
IM
Grants
NIAMS NIH HHS · AR42689 · United States
NHLBI NIH HHS · HL56949 · United States
NHLBI NIH HHS · HL54936 · United States
NHLBI NIH HHS · HL62524 · United States
Corrections
CommentIn
PMID: 11696603
External Links
PubMed source DOI: 10.1084/jem.194.9.1361 PMC Full Text View journal details
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