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Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment.

Janatpour MJ, Hudak S, Sathe M, Sedgwick JD, McEvoy LM - J. Exp. Med. (2001)

Bottom Line: 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] mice) expressed MIG and this subset of HEVs preferentially supported monocyte binding.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.

View Article: PubMed Central - PubMed

Affiliation: DNAX Research Institute, Inc., Palo Alto, CA 94304, USA.

ABSTRACT
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] 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.

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Newly recruited monocytes express CXCR3. Balb/C mice were given a single intraperitoneal injection of thyoglycollate. 2 d later, peritoneal cells were harvested and stained for CXCR3 or an isotype control (CyC), CD11b (FITC), F4/80 (PE), and GR1 (APC). Gates were set on newly recruited monocytes (CD11b+) and neutrophils (GR1+), after selection based on size and side-scatter. A significant percentage of monocytes recruited to the peritoneum expressed CXCR3 (compared to isotype control) whereas the neutrophil population did not.
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fig6: Newly recruited monocytes express CXCR3. Balb/C mice were given a single intraperitoneal injection of thyoglycollate. 2 d later, peritoneal cells were harvested and stained for CXCR3 or an isotype control (CyC), CD11b (FITC), F4/80 (PE), and GR1 (APC). Gates were set on newly recruited monocytes (CD11b+) and neutrophils (GR1+), after selection based on size and side-scatter. A significant percentage of monocytes recruited to the peritoneum expressed CXCR3 (compared to isotype control) whereas the neutrophil population did not.

Mentions: Together these data prompted us to ask whether newly recruited monocytes express CXCR3. To obtain an enriched population of recruited monocytes, mice were injected with thyoglycollate intraperitoneally and the elicited cells were harvested by peritoneal lavage. Cells were stained for CXCR3, CD11b, F4/80. and GR1 and analyzed by FACSĀ®. As shown in Fig. 6 , a significant percentage of the newly recruited monocytes express CXCR3, as compared with the isotype control and GR1+ neutrophils.


Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment.

Janatpour MJ, Hudak S, Sathe M, Sedgwick JD, McEvoy LM - J. Exp. Med. (2001)

Newly recruited monocytes express CXCR3. Balb/C mice were given a single intraperitoneal injection of thyoglycollate. 2 d later, peritoneal cells were harvested and stained for CXCR3 or an isotype control (CyC), CD11b (FITC), F4/80 (PE), and GR1 (APC). Gates were set on newly recruited monocytes (CD11b+) and neutrophils (GR1+), after selection based on size and side-scatter. A significant percentage of monocytes recruited to the peritoneum expressed CXCR3 (compared to isotype control) whereas the neutrophil population did not.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195975&req=5

fig6: Newly recruited monocytes express CXCR3. Balb/C mice were given a single intraperitoneal injection of thyoglycollate. 2 d later, peritoneal cells were harvested and stained for CXCR3 or an isotype control (CyC), CD11b (FITC), F4/80 (PE), and GR1 (APC). Gates were set on newly recruited monocytes (CD11b+) and neutrophils (GR1+), after selection based on size and side-scatter. A significant percentage of monocytes recruited to the peritoneum expressed CXCR3 (compared to isotype control) whereas the neutrophil population did not.
Mentions: Together these data prompted us to ask whether newly recruited monocytes express CXCR3. To obtain an enriched population of recruited monocytes, mice were injected with thyoglycollate intraperitoneally and the elicited cells were harvested by peritoneal lavage. Cells were stained for CXCR3, CD11b, F4/80. and GR1 and analyzed by FACSĀ®. As shown in Fig. 6 , a significant percentage of the newly recruited monocytes express CXCR3, as compared with the isotype control and GR1+ neutrophils.

Bottom Line: 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] mice) expressed MIG and this subset of HEVs preferentially supported monocyte binding.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.

View Article: PubMed Central - PubMed

Affiliation: DNAX Research Institute, Inc., Palo Alto, CA 94304, USA.

ABSTRACT
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] 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.

Show MeSH
Related in: MedlinePlus