Hemoglobin-vesicles as oxygen carriers

Influence on phagocytic activity and histopathological changes in reticuloendothelial system

Hiromi Sakai, Hirohisa Horinouchi, Kenichi Tomiyama, Eiji Ikeda, Shinji Takeoka, Koichi Kobayashi, Eishun Tsuchida

    Research output: Contribution to journalArticle

    82 Citations (Scopus)

    Abstract

    Hemoglobin-vesicles (HbV) have been developed for use as artificial oxygen carriers (particle diameter, 250 nm) in which a purified Hb solution is encapsulated with a phospholipid bilayer membrane. The influence of HbV on the reticuloendothelial system was studied by carbon clearance measurements and histopathological examination. The HbV suspension ([Hb] = 10 g/dl) was intravenously infused in male Wistar rats at dose rates of 10 and 20 ml/kg, and the phagocytic activity was measured by monitoring the rate of carbon clearance at 8 hours and at 1, 3, 7, and 14 days after infusion. The phagocytic activity transiently decreased one day after infusion by about 40%, but it recovered and was enhanced at 3 days, showing a maximum of about twice the quiescent level at 7 days, and then returned to the normal value at 14 days. The initial transient decreased activity indicates a partly, but not completely, suppressed defensive function of the body. The succeeding increased phagocytic activity corresponds to the increased metabolism of HbV. The histopathological examination with anti-human Hb antibody, hematoxylin/eosin, and oil red O stainings showed that HbV was metabolized within 7 days. Hemosiderin was very slightly confirmed with Berlin blue staining at 3 and 7 days in liver and spleen, though they completely disappeared at 14 days, indicating that the heme metabolism, excretion or recycling of iron proceeded smoothly and iron deposition was minimal. Electron microscopic examination of the spleen and liver tissues clearly demonstrated the particles of HbV with a diameter of about 1/40 of red blood cells in capillaries, and in phagosomes as entrapped in the spleen macrophages and Kupffer cells one day after infusion. The vesicular structure could not be observed at 7 days. Even though the infusion of HbV modified the phagocytic activity for 2 weeks, it does not seem to cause any irreversible damage to the phagocytic organs. These results offer important information for evaluating the safety issues of HbV for clinical use.

    Original languageEnglish
    Pages (from-to)1079-1088
    Number of pages10
    JournalAmerican Journal of Pathology
    Volume159
    Issue number3
    Publication statusPublished - 2001

    Fingerprint

    Mononuclear Phagocyte System
    Hemoglobins
    Oxygen
    Spleen
    Carbon
    Iron
    Staining and Labeling
    Hemosiderin
    Phagosomes
    Kupffer Cells
    Liver
    Recycling
    Hematoxylin
    Eosine Yellowish-(YS)
    Heme
    Wistar Rats
    Phospholipids
    Suspensions
    Reference Values
    Erythrocytes

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

    Cite this

    Hemoglobin-vesicles as oxygen carriers : Influence on phagocytic activity and histopathological changes in reticuloendothelial system. / Sakai, Hiromi; Horinouchi, Hirohisa; Tomiyama, Kenichi; Ikeda, Eiji; Takeoka, Shinji; Kobayashi, Koichi; Tsuchida, Eishun.

    In: American Journal of Pathology, Vol. 159, No. 3, 2001, p. 1079-1088.

    Research output: Contribution to journalArticle

    Sakai, H, Horinouchi, H, Tomiyama, K, Ikeda, E, Takeoka, S, Kobayashi, K & Tsuchida, E 2001, 'Hemoglobin-vesicles as oxygen carriers: Influence on phagocytic activity and histopathological changes in reticuloendothelial system', American Journal of Pathology, vol. 159, no. 3, pp. 1079-1088.
    Sakai, Hiromi ; Horinouchi, Hirohisa ; Tomiyama, Kenichi ; Ikeda, Eiji ; Takeoka, Shinji ; Kobayashi, Koichi ; Tsuchida, Eishun. / Hemoglobin-vesicles as oxygen carriers : Influence on phagocytic activity and histopathological changes in reticuloendothelial system. In: American Journal of Pathology. 2001 ; Vol. 159, No. 3. pp. 1079-1088.
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    abstract = "Hemoglobin-vesicles (HbV) have been developed for use as artificial oxygen carriers (particle diameter, 250 nm) in which a purified Hb solution is encapsulated with a phospholipid bilayer membrane. The influence of HbV on the reticuloendothelial system was studied by carbon clearance measurements and histopathological examination. The HbV suspension ([Hb] = 10 g/dl) was intravenously infused in male Wistar rats at dose rates of 10 and 20 ml/kg, and the phagocytic activity was measured by monitoring the rate of carbon clearance at 8 hours and at 1, 3, 7, and 14 days after infusion. The phagocytic activity transiently decreased one day after infusion by about 40{\%}, but it recovered and was enhanced at 3 days, showing a maximum of about twice the quiescent level at 7 days, and then returned to the normal value at 14 days. The initial transient decreased activity indicates a partly, but not completely, suppressed defensive function of the body. The succeeding increased phagocytic activity corresponds to the increased metabolism of HbV. The histopathological examination with anti-human Hb antibody, hematoxylin/eosin, and oil red O stainings showed that HbV was metabolized within 7 days. Hemosiderin was very slightly confirmed with Berlin blue staining at 3 and 7 days in liver and spleen, though they completely disappeared at 14 days, indicating that the heme metabolism, excretion or recycling of iron proceeded smoothly and iron deposition was minimal. Electron microscopic examination of the spleen and liver tissues clearly demonstrated the particles of HbV with a diameter of about 1/40 of red blood cells in capillaries, and in phagosomes as entrapped in the spleen macrophages and Kupffer cells one day after infusion. The vesicular structure could not be observed at 7 days. Even though the infusion of HbV modified the phagocytic activity for 2 weeks, it does not seem to cause any irreversible damage to the phagocytic organs. These results offer important information for evaluating the safety issues of HbV for clinical use.",
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