Dataset Information

Alveolar macrophages lack CCR2 expression and do not migrate to CCL2.

ABSTRACT: BACKGROUND:The recruitment of mononuclear cells has important implications for tissue inflammation. Previous studies demonstrated enhanced CCR1 and CCR5 expression and decreased CCR2 expression during in vitro monocyte to macrophage differentiation. To date, no study examined the in vivo differences in chemokine receptor expression between human peripheral blood monocytes and alveolar macrophages. METHODS:We examined the expression of these receptors in human peripheral blood monocytes and alveolar macrophages using microarray analysis, reverse-transcriptase PCR, flow cytometry and migration analyses. RESULTS:In contrast to peripheral blood monocytes, alveolar macrophages did not express the CCL2 receptor, CCR2, and did not migrate toward CCL2. In contrast, monocytes and freshly isolated resident alveolar macrophages both migrated towards CCL3. However, up to 6-fold more monocytes migrated toward equivalent concentrations of CCL3 than did alveolar macrophages from the same donor. While peripheral blood monocytes expressed the CCL3 receptor, CCR1, alveolar macrophages expressed the alternate CCL3 receptor, CCR5. The addition of anti-CCR5 blocking antibodies completely abrogated CCL3-induced migration in alveolar macrophages, but did not affect the migration of peripheral blood monocytes. CONCLUSION:These data support the specificity of CCL2 to selectively drive monocyte, but not alveolar macrophage recruitment to the lung and CCR5 as the primary macrophage receptor for CCL3.

SUBMITTER: Opalek JM

PROVIDER: S-EPMC2099427 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Alveolar macrophages lack CCR2 expression and do not migrate to CCL2.

Opalek Judy M JM Ali Naeem A NA Lobb Jennifer M JM Hunter Melissa G MG Marsh Clay B CB

Journal of inflammation (London, England) 20070922

<h4>Background</h4>The recruitment of mononuclear cells has important implications for tissue inflammation. Previous studies demonstrated enhanced CCR1 and CCR5 expression and decreased CCR2 expression during in vitro monocyte to macrophage differentiation. To date, no study examined the in vivo differences in chemokine receptor expression between human peripheral blood monocytes and alveolar macrophages.<h4>Methods</h4>We examined the expression of these receptors in human peripheral blood mono ...[more]

PMID: 17888174

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Project description:Objective: The present study investigated the roles and underlying mechanism of CCL2/CCR2 axis in the interactions between tumor cells and tumor-associated macrophages (TAMs) during the progression of salivary adenoid cystic carcinoma (SACC). Methods: Immunohistochemical staining and survival analysis were performed to study the correlation and clinical value of CD68, CD163, CCL2, and CCR2 expression in SACC cases. CCL2 silencing by RNA interference and CCR2 blocking by CCR2 specific antagonist (RS504393) were performed. ELISA, qRT-PCR, western blot, immunofluorescence, flow cytometry, CCK8, scratch wound healing, and transwell assays were used to explore the functional roles and possible mechanism of CCL2/CCR2 axis in the interactions between SACC cells and TAMs. The effects of targeting TAMs by blocking the CCL2/CCR2 axis were investigated in a xenograft mice model with SACC cells. Results: The high infiltration of TAMs marked by CD68 and high infiltration of M2 TAMs marked by CD163 were significantly correlated with the expression of CCL2 and CCR2 in SACC tissues. Notably, the high infiltration of TAMs and the overexpression of CCL2 were obviously associated with the clinical progression and poor prognosis of SACC. SACC cells derived CCL2 could activate its receptor CCR2 expression in TAMs in vitro. The in vitro results further indicated that the SACC cells derived CCL2 was involved in the recruitment, M2 polarization, and GDNF expression of TAMs through the CCL2/CCR2 axis. Meanwhile, TAMs derived GDNF promoted the proliferation, migration, and invasion of SACC cells through the GDNF/p-RET pathway. Treating immunodeficient mice with the CCR2 antagonist (RS504393) greatly inhibited the infiltration of TAMs and the tumorigenicity of SACC cells. Conclusion: These new findings indicated that the CCL2/CCR2 axis promoted the progression of SACC cells via recruiting and reprogramming TAMs. Targeting TAMs by blocking the CCL2/CCR2 axis might be a prospective strategy for SACC therapy.

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Alveolar macrophages lack CCR2 expression and do not migrate to CCL2.

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Alveolar macrophages lack CCR2 expression and do not migrate to CCL2.

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