Kooguchi K, Hashimoto S, Kobayashi A, Kitamura Y, Kudoh I, Wiener-Kronish J, Sawa,T.
Role of alveolar macrophages in initiation and regulation of inflammation in Pseudomonas aeruginosa pneumonia.
Infect. Immun. 1998 Jul;66(7):3164–9.
[toggle_content title=”Abstract”] To evaluate the role of alveolar macrophages (AMs) in acute Pseudomonas aeruginosa pneumonia in mice, AMs were depleted by aerosol inhalation of liposomes containing clodronate disodium. AM-depleted mice were then intratracheally infected with 5 x 105 CFU of P. aeruginosa . In addition to monitoring neutrophil recruitment and chemokine releases, lung injury was evaluated soon after infection (8 h) and at a later time (48 h). At 8 h, depletion of AMs reduced neutrophil recruitment, chemokine release, and lung injury. At 48 h, however, depletion of AMs decreased bacterial clearance and resulted in delayed movement of neutrophils from the site of inflammation with aggravated lung injury. With instillation of 5 x 107 CFU of bacteria, AM-depleted mice showed low mortality within 24 h of infection but high mortality at a later time, in contrast to non-AM-depleted mice. These results demonstrate that depletion of AMs has beneficial early effects but deleterious late effects on lung injury and survival in cases of P. aeruginosa pneumonia.
[/toggle_content] [toggle_content title=”Clodronate Liposome Parameters”] [custom_table]
Clodronate Concentration Total Lipid Concentration Lipid Composition Lipid Mole % Liposome Type Control Liposomes
not stated 11 mg/ml EPC/Chol 57/43 REV none
[/custom_table] [/toggle_content] [toggle_content title=”Animals and Dosing”] [custom_table]
Animal Description Clodronate Dose Dosing Site/Method Target Phagocytes Systemic Dosing? Systemic Results
CD-1, male, 35-37 g not stated aerosol / lungs alveolar macrophages (AM) no not evaluated
[/custom_table] [/toggle_content] [toggle_content title=”Notes”]
  1. Authors state that liposomes were prepared as in Publication 1, however lipid composition is different as is final volume. Encapsulated clodronate is not published. Lipid concentration calculated assuming 100% recovery.
  2. As discussed for publication 1., passing liposomes through a syringe filter is not equivalent to extrusion.
  3. Aerotech II nebulizer at 12 L/min. No further details published.
[/toggle_content] [toggle_content title=”Results”]
  1. >95% of the AM were depleted (BAL cell counts via light microscopy).
  2. No neutrophils at t=0 post-innoculation, therefore neutrophilia is not observed in this model.
  3. No control liposomes dosed; could chemokine levels be altered by liposomes alone? Not likely but important control.