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Publication : Molecular imaging of folate receptor β-positive macrophages during acute lung inflammation.

First Author  Han W Year  2015
Journal  Am J Respir Cell Mol Biol Volume  53
Issue  1 Pages  50-9
PubMed ID  25375039 Mgi Jnum  J:318249
Mgi Id  MGI:6858917 Doi  10.1165/rcmb.2014-0289OC
Citation  Han W, et al. (2015) Molecular imaging of folate receptor beta-positive macrophages during acute lung inflammation. Am J Respir Cell Mol Biol 53(1):50-9
abstractText  Characterization of markers that identify activated macrophages could advance understanding of inflammatory lung diseases and facilitate development of novel methodologies for monitoring disease activity. We investigated whether folate receptor beta (FRbeta) expression could be used to identify and quantify activated macrophages in the lungs during acute inflammation induced by Escherichia coli LPS. We found that FRbeta expression was markedly increased in lung macrophages at 48 hours after intratracheal LPS. In vivo molecular imaging with a fluorescent probe (cyanine 5 polyethylene glycol folate) showed that the fluorescence signal over the chest peaked at 48 hours after intratracheal LPS and was markedly attenuated after depletion of macrophages. Using flow cytometry, we identified the cells responsible for uptake of cyanine 5-conjugated folate as FRbeta(+) interstitial macrophages and pulmonary monocytes, which coexpressed markers associated with an M1 proinflammatory macrophage phenotype. These findings were confirmed using a second model of acute lung inflammation generated by inducible transgenic expression of an NF-kappaB activator in airway epithelium. Using CC chemokine receptor 2-deficient mice, we found that FRbeta(+) macrophage/monocyte recruitment was dependent on the monocyte chemotactic protein-1/CC chemokine receptor 2 pathway. Together, our results demonstrate that folate-based molecular imaging can be used as a noninvasive approach to detect classically activated monocytes/macrophages recruited to the lungs during acute inflammation.
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