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L-FABP is exclusively expressed in alveolar macrophages within the myeloid lineage: evidence for a
Christian Schachtrup1, Thomas E Scholzen, Veronika Grau
1Department of Biochemistry, University of Münster, Münster, Germany.
Abstract:
Peroxisome proliferator-activated receptors (PPARs) play a role in inflammation and, in particular, PPARgamma is involved in monocyte/macrophage differentiation. Members of the fatty acid-binding protein (FABP) family have been reported to function as transactivators for PPARs. Therefore, the expression of PPARs and FABPs in the myeloid lineage was investigated by real-time PCR and immunofluorescence analysis. We found adipocyte-, epidermal-, and heart-type FABP to be ubiquitously expressed within the myeloid lineage. In contrast, liver-type FABP was exclusively detected in murine alveolar macrophages (AM), confirmed on protein level by double fluorescence analysis. The PPAR subtypes also showed a temporally and spatially regulated expression pattern in myeloid cells: the beta-subtype was expressed in bone marrow, peritoneal, and alveolar macrophages, whereas it was not detected in dendritic cells (DCs). The gamma1-isoform was present in all cells, however, at different levels, whereas the gamma2-isoform was expressed in alveolar macrophages and dendritic cells. A low level PPARalpha mRNA could be detected in peritoneal macrophages and immature dendritic cells but not in mature dendritic cells and bone marrow macrophages. Interestingly, PPARalpha mRNA was also absent in the alveolar macrophages although liver-type FABP was expressed, indicating that gene expression of liver-type FABP was independent of PPARalpha. Since liver-type FABP is known as transactivator of PPARgamma the simultaneous expression of both proteins may have general implications for the activation of PPARgamma in alveolar macrophages.
Insights
Fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptors (PPARs) are key in myeloid cell function. Liver-type FABP and PPARgamma are co-expressed in alveolar macrophages, suggesting a role in PPARgamma activation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Peroxisome proliferator-activated receptors (PPARs) regulate inflammation and monocyte/macrophage differentiation.
- Fatty acid-binding proteins (FABPs) can act as transactivators for PPARs.
Purpose of the Study:
- To investigate the expression of PPARs and FABPs in the myeloid lineage.
- To understand the relationship between liver-type FABP and PPARalpha/gamma expression in macrophages.
Main Methods:
- Real-time PCR was used to analyze gene expression.
- Immunofluorescence analysis confirmed protein expression.
- Myeloid cell subtypes including alveolar macrophages and dendritic cells were studied.
Main Results:
- Adipocyte-, epidermal-, and heart-type FABPs were ubiquitously expressed in myeloid cells.
- Liver-type FABP was exclusively found in murine alveolar macrophages (AM).
- PPAR subtypes showed distinct expression patterns across myeloid cells; PPARgamma1 was ubiquitous, gamma2 in AM and dendritic cells (DCs).
- PPARalpha was detected in some myeloid cells but absent in AM, despite liver-type FABP expression, indicating PPARalpha-independent FABP gene expression.
- Co-expression of liver-type FABP and PPARgamma in AM was observed.
Conclusions:
- Liver-type FABP is specifically expressed in alveolar macrophages.
- The expression of PPAR subtypes is spatially and temporally regulated within the myeloid lineage.
- The co-expression of liver-type FABP and PPARgamma in alveolar macrophages suggests a significant role in PPARgamma activation within these cells.
