Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment.
Monocytes recruited from the blood are key contributors to the nature of an immune response. While monocyte recruitment in a subset of immunopathologies has been well studied and largely attributed to the chemokine monocyte chemoattractant protein (MCP)-1, mechanisms mediating such recruitment to other sites of inflammation remain elusive. Here, we showed that localized inflammation resulted in an increased binding of monocytes to perifollicular high endothelial venules (HEVs) of lymph nodes draining a local inflammatory site. Quantitative PCR analyses revealed the upregulation of many chemokines in the inflamed lymph node, including MCP-1 and MIG. HEVs did not express detectable levels of MCP-1; however, a subset of HEVs in inflamed lymph nodes in wild-type (but not tumor necrosis factor [TNF] null mice) expressed MIG and this subset of HEVs preferentially supported monocyte binding. Expression of CXCR3, the receptor for MIG, was detected on a small subset of peripheral blood monocytes and on a significant percentage of recruited monocytes. Most importantly, in both ex vivo and in vivo assays, neutralizing anti-MIG antibodies blocked monocyte binding to inflamed lymph node HEVs. Together, these results suggest that the lymph node microenvironment can dictate the nature of molecules expressed on HEV subsets in a TNF-dependent fashion and that inflammation-induced MIG expression by HEVs can mediate monocyte recruitment.
Janatpour
M J
MJ
DNAX Research Institute, Inc., Palo Alto, CA 94304, USA.
Hudak
S
S
Sathe
M
M
Sedgwick
J D
JD
McEvoy
L M
LM
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics*; D004729:Endothelium, Lymphatic / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D018932:Chemokine CCL2; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha