Molecular imaging of folate receptor β-positive macrophages during acute lung inflammation.
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 β (FRβ) expression could be used to identify and quantify activated macrophages in the lungs during acute inflammation induced by Escherichia coli LPS. We found that FRβ 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 FRβ(+) 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-κB activator in airway epithelium. Using CC chemokine receptor 2-deficient mice, we found that FRβ(+) 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.
1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Wei
W
Han
1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Rinat
R
Zaynagetdinov
2 Department of Cancer Biology.
Fiona E
FE
Yull
1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Vasiliy V
VV
Polosukhin
1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Linda A
LA
Gleaves
1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Harikrishna
H
Tanjore
1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.|3 Division of Pulmonary Medicine, Department of Pediatrics.
Lisa R
LR
Young
4 Department of Radiology and Radiological Sciences.|5 Institute of Imaging Science, and.
Todd E
TE
Peterson
4 Department of Radiology and Radiological Sciences.|5 Institute of Imaging Science, and.
H Charles
HC
Manning
6 Division of Neonatology, Department of Pediatrics, University of California, San Diego, La Jolla, California; and.
Lawrence S
LS
Prince
1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.|2 Department of Cancer Biology.|7 Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.|8 Department of Veterans Affairs Medical Center, Nashville, Tennessee.
Timothy S
TS
Blackwell
D000208:Acute Disease; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry; D005456:Fluorescent Dyes / Q000494:pharmacology; D058976:Folate Receptor 2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism
C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D005456:Fluorescent Dyes; D058976:Folate Receptor 2; D008070:Lipopolysaccharides; D054390:Receptors, CCR2
acute lung inflammation; folate receptor β; macrophage; molecular imaging