Depletion of alveolar macrophages by liposome-encapsulated dichloromethylene diphosphonate.
Alveolar macrophages (AM) play an important role in lung biology. In this study, we demonstrated that tracheal insufflation of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP-liposome) selectively depleted AMs in rats. Insufflation of a single dose of Cl2MDP-liposomes (80 microliters containing 1.34 mumol of Cl2MDP) but not liposomes containing phosphate-buffered saline resulted in > 70% depletion of AMs starting within 1 day and lasting for > 5 days after insufflation. There was a slight but significant intraalveolar inflammatory response. Insufflation of Cl2MDP also resulted in depletion of AMs; however, it caused cytoplasmic edema of alveolar epithelial cells as well. Depletion of AMs by Cl2MDP-liposomes markedly reduced the endotoxin-induced neutrophil (polymorphonuclear lymphocyte) recruitment and the release of tumor necrosis factor into the alveolar space, suggesting that endotoxin-induced neutrophil recruitment and tumor necrosis factor release were dependent on AMs. This AM-depleted animal model will be useful for studying the in vivo functions of AMs and their role in various physiological and pathological conditions.
Berg
J T
JT
Research Service, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, New York.
Lee
S T
ST
Thepen
T
T
Lee
C Y
CY
Tsan
M F
MF
D000818:Animals; D002452:Cell Count; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea
D008081:Liposomes; D004002:Clodronic Acid