TY - JOUR
T1 - Alveolar macrophage ingestion and phagosome-lysosome fusion defect associated with virus pneumonia
AU - Jakab, G. J.
AU - Warr, G. A.
AU - Sannes, P. L.
PY - 1980
Y1 - 1980
N2 - Virus-induced suppression of pulmonary phagocytic defenses is associated with defects in the intracellular processing of bacteria by alveolar macrophages. To determine whether the intracellular defect is related to a failure in phagosomelysosome fusion, mice were infected with a sublethal dose of Sendai virus, and the capacity of phagocytic cells, obtained by lung lavage, to exhibit phagosome-lysosome fusion was quantitated during the course of the viral infection. Lysosomes of alveolar macrophages were prelabeled with acridine orange, the cells were challenged with Candida krusei, and fusion was determined with fluorescence microscopy by the discharge of the dye into the yeast-containing phagosome. Ultrastructural cytochemical studies verified the validity of the fluorescent fusion assay. Simultaneous experiments were performed to determine whether the viral infection also suppressed phagocytic ingestion by alveolar macrophages. Phagosome-lysosome fusion was progressively inhibited during the viral infection, reaching a low at day 7 when only 13 ± 3% of the phagocytic cells fused as compared with 97 ± 3% in cells from uninfected control animals; respectively, 55 ± 5% as compared with 74 ± 2% of the phagocytic cells contained yeasts. Thereafter, phagosome-lysosome fusion progressively increased reaching near normal levels (92 ± 3%) on day 17 of the infection. At the same time period, phagocytic uptake was enhanced to a level where 97 ± 3% of the cells contained yeasts. These data demonstrated that virus-induced suppression of intrapulmonary killing of bacteria involves functional lesions that retard the ingestion of inhaled organisms by alveolar macrophages and inhibit intracellular processing by degradative lysosomal enzymes by interfering with phagosome-lysosome fusion.
AB - Virus-induced suppression of pulmonary phagocytic defenses is associated with defects in the intracellular processing of bacteria by alveolar macrophages. To determine whether the intracellular defect is related to a failure in phagosomelysosome fusion, mice were infected with a sublethal dose of Sendai virus, and the capacity of phagocytic cells, obtained by lung lavage, to exhibit phagosome-lysosome fusion was quantitated during the course of the viral infection. Lysosomes of alveolar macrophages were prelabeled with acridine orange, the cells were challenged with Candida krusei, and fusion was determined with fluorescence microscopy by the discharge of the dye into the yeast-containing phagosome. Ultrastructural cytochemical studies verified the validity of the fluorescent fusion assay. Simultaneous experiments were performed to determine whether the viral infection also suppressed phagocytic ingestion by alveolar macrophages. Phagosome-lysosome fusion was progressively inhibited during the viral infection, reaching a low at day 7 when only 13 ± 3% of the phagocytic cells fused as compared with 97 ± 3% in cells from uninfected control animals; respectively, 55 ± 5% as compared with 74 ± 2% of the phagocytic cells contained yeasts. Thereafter, phagosome-lysosome fusion progressively increased reaching near normal levels (92 ± 3%) on day 17 of the infection. At the same time period, phagocytic uptake was enhanced to a level where 97 ± 3% of the cells contained yeasts. These data demonstrated that virus-induced suppression of intrapulmonary killing of bacteria involves functional lesions that retard the ingestion of inhaled organisms by alveolar macrophages and inhibit intracellular processing by degradative lysosomal enzymes by interfering with phagosome-lysosome fusion.
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U2 - 10.1128/iai.27.3.960-968.1980
DO - 10.1128/iai.27.3.960-968.1980
M3 - Article
C2 - 6247283
AN - SCOPUS:0018877098
SN - 0019-9567
VL - 27
SP - 960
EP - 968
JO - Infection and immunity
JF - Infection and immunity
IS - 3
ER -