Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep

Miyamoto, K., Schultz, E., Heath, T., Mitchell, M.D., Albertine, K.H. and Staub, N.C. (1988) Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep. Journal of Applied Physiology, 64 3: 1143-1152.


Author Miyamoto, K.
Schultz, E.
Heath, T.
Mitchell, M.D.
Albertine, K.H.
Staub, N.C.
Title Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep
Journal name Journal of Applied Physiology   Check publisher's open access policy
ISSN 1522-1601
8750-7587
Publication date 1988-03-01
Year available 1988
Sub-type Article (original research)
Open Access Status Not yet assessed
Volume 64
Issue 3
Start page 1143
End page 1152
Total pages 10
Place of publication Bethesda, MD, U.S.A.
Publisher American Physiological Society
Language eng
Subject 1103 Clinical Sciences
1102 Cardiovascular Medicine and Haematology
Formatted abstract
We studied the effects of liposomes on the pulmonary circulation of sheep and found a close correlation between liposome retention in the lung and the intravascular macrophages. A test dose of liposomes (5.5 μmol of total lipids) injected intravenously transiently increased pulmonary arterial pressure from 24 ± 2 to 55 ± 16 (SD) cmH2O. The pulmonary arterial pressure responses were dose dependent and reproducible. The rise in pulmonary arterial pressure was blocked completely by indomethacin and 75% by a thromboxane synthase inhibitor. Systemic arterial thromboxane B2 concentration increased from a base-line level of < 50 pg/ml to 250 ± 130 pg/ml at the peak of the pressor response. Larger doses of liposomes (220 μol of total lipids) infused intravenously over 1 h increased pulmonary arterial pressure maximally within the first 15 min. Lymph flow increased and lymph protein concentration decreased, suggesting venoconstriction. Over half (62.4 ± 15.7%) of 111In-labeled liposomes remained in the lung after 2 h. Fluorescence and transmission electron microscopy showed that > 90% of the liposomes were associated with mononuclear cells in the lumen of the alveolar wall microvessels. We conclude that liposomes affect pulmonary arterial pressure transiently by a mechanism involving the arachidonate cascade, principally thromboxane. Our observations suggest that a population of pulmonary intravascular macrophages is likely to be the source of the thromboxane and the pulmonary hemodynamic and lymph dynamic changes that occur in a dose-dependent fashion, although interactions between liposomes, leukocytes, or endothelial cells, in addition to the macrophages, have not been completely ruled out. We believe this is the first demonstration that pulmonary intravascular macrophages may be the source of the arachidonate metabolites rather than endothelial cells, neutrophils, or perivascular interstitial cells.
Keyword Physiology
Sport Sciences
Physiology
Sport Sciences
PHYSIOLOGY
SPORT SCIENCES
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID HL-19737
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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