Effect of particles on sheep lung hemodynamics parallels depletion and recovery of intravascular macrophages.
We previously showed in newborn lambs that the pulmonary hemodynamic responses to foreign particulate matter (liposomes; Monastral blue) developed in parallel with the maturation of the pulmonary intravascular macrophage system. We now report our use of the liposome-encapsulated heavy-metal-chelating agent dichloromethylene diphosphonate to deplete the intravascular macrophages of small lambs. Functionally and by quantitative histology, we depleted the vast majority of the intravascular macrophages (71% by Monastral blue particle retention, n = 22; 77% by histology; n = 2). Depletion success increased to > 90% as we optimized the liposome-depletion regime. Recovery of the lung hemodynamic response began within 3 days. By 2 wk, the functional responses had fully recovered (n = 8), and, according to quantitative histology, the macrophage population (n = 2) had recovered 65%. Macrophage depletion in lambs is relatively inexpensive and easy to achieve. It is a safe procedure and is followed by full recovery in approximately 2 wk, provided that an aseptic technique is used to prevent bacteremia.
Sone
Y
Y
Cardiovascular Research Institute, University of California, San Francisco 94143, USA.
Nicolaysen
A
A
Staub
N C
NC
D018712:Analgesics, Non-Narcotic / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001794:Blood Pressure / Q000502:physiology; D002196:Capillaries / Q000473:pathology; D004002:Clodronic Acid / Q000737:chemistry / Q000494:pharmacology; D005549:Foreign-Body Reaction / Q000473:pathology / Q000503:physiopathology*; D008081:Liposomes; D008168:Lung / Q000166:cytology / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000187:drug effects; D011652:Pulmonary Circulation / Q000502:physiology*; D012756:Sheep
D018712:Analgesics, Non-Narcotic; D008081:Liposomes; D004002:Clodronic Acid