1997 Fiscal Year Final Research Report Summary
Inter-cellular signal transduction by alveolar macrophages in acute lung injury
| Project/Area Number |
07407045
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
HASHIMOTO Satoru Kyoto Prefectural University of Medicine, Anesthesiology, Associate professor, 医学部, 助教授 (90167578)
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| Co-Investigator(Kenkyū-buntansha) |
KUDOH Ichidai Yokohama University of Medicine, Anesthesiology, Associate professor, 医学部, 助教授 (30145700)
KOBAYASHI Atsuko Kyoto Prefectural University of Medicine, Anesthesiology, Assistant professor, 医学部, 助手 (70264778)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Acute lung injury / Acute respiratory distress syndrome / Alveolar macrophaphage / iNOS / Inflammatory cytokine |
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| Research Abstract |
To examine the role of alveolar macrophages (AMs) in initial PMN recruitment after Gram-negative bacterial infection, we depleted AMs in rodent by aerosol inhalation of negatively charged large oligolamellar liposomes encapsulating clodronate disodium (Cl2MDP-liposomes). This method cleared over 95% of AMs from the lungs without causing lung damage or airspace neutrophilia. Depletion of AMS attenuated initial PMN recruitment and chemokine production in Pseudomonas aeruginosa pneumonia in rats. To further evaluate the role of AMs in acute and subacute Pseudomonas aeruginosa pneumonia in mice, AM-depleted mice and control mice were compared after intratracheally infected by P. aeruginosa. In addition to monitoring neutrophils recrutiment and chemokine releases, lung injury was evaluated soon after infection (8 h) and a later time (48 h). At 8 h, depletion of AMs reduced neutrophils recrutiment, 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. In the setting of 50% lethal amount of bacteria instillation in control mice, the survival rate of AM-depleted mice showed low mortality within 24 h of infecton, but high mortality. at 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 P. aeruginosa pneumonia.
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