Rigors with vancomycin.
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Drug Contamination↗
Biomedical subjects
N S Conley
Publications and source records attributed to N S Conley.
Subpopulation of alveolar macrophages inhibits superoxide anion production by macrophages.
Pig alveolar macrophages are a heterogeneous population of cells. Three subpopulations or bands exist when the whole population is separated according to density. Band 1 cells are the least dense cells and constitute 9% of the total population. Bands 2 and 3 represent 44 and 47% of the total population. The three subpopulations generate superoxide anions, although to varying degrees. Band 3 cells are the most active, while band 1 cells are the least active. The amount of superoxide anions released in a mixed population of bands 1, 2, and 3 cells was less than the sum of that produced from each band assayed separately. Band 1 cells were found to inhibit by 47% the production of superoxide anions by band 3 cells. Conditioned medium from band 1 cells contains a heat-sensitive, nondialyzable, soluble factor responsible for this inhibition.
Animals↗
Bleomycin increases superoxide production in the most active alveolar macrophage subpopulation.
Pig alveolar macrophages were separated into three subpopulations by density centrifugation. The most dense subpopulation of macrophages had the greatest rate of superoxide anion production of 4.4 +/- 2.6 nmol/1 x 10(6) cells/min. Bleomycin had its greatest effect on this subpopulation by increasing the rate by nearly 100% in cells stimulated with phorbol myristate acetate or phorbol dibutyrate. Bleomycin increased the maximum rate of superoxide production without changing the apparent Km of 0.012 microgram/ml. Bleomycin did not quantitatively effect phorbol dibutyrate binding to alveolar macrophages. The cells have 9.1 +/- 1.0 x 10(5) sites/cell with a KD of 16 nmol. Results indicate that bleomycin may enhance superoxide production by effecting steps distal to protein kinase C in the superoxide anion production pathway.
Animals↗
Superoxide generation by pig alveolar macrophages.
Pig alveolar macrophages generate superoxide anions at a rate of 1.8 nanomoles/1 X 10(6) cells/min. The intracellular value of ATP in resting cells was 4.0 +/- 0.1 X 10(-16) mole/cell; in contrast the value in cells generating superoxide anions was 2.0 +/- 0.6. Superoxide generation was increasingly inhibited by exposing cells to adenosine from 0.1 to 1.0 mM. Unlike human macrophages, pig cell production of superoxide anions was not inhibited by exposure to the adenosine analog, 2-Cl-adenosine.
2-Chloroadenosine↗
Bleomycin increases superoxide anion generation by pig peripheral alveolar macrophages.
Pulmonary fibrosis is the major toxic effect of bleomycin chemotherapy; however, the molecular mechanisms of the pathological process are unknown. Since alveolar macrophages produce toxic oxygen metabolites and these can damage lung cells, the effect of bleomycin on superoxide anion production was investigated in subpopulations of pig alveolar macrophages. Cells were lavaged from the lung and separated into three subpopulations according to their density. Their capacity to generate superoxide anions increased the more distally they were located. Bleomycin (5.0 milliunits/ml) increased the rate of superoxide production by 75 +/- 24% in dense alveolar macrophages located in the lung periphery. Hydrocortisone (10.0 micrograms/ml) inhibited this superoxide production by 33 +/- 10%. Results from this study suggest that an excess production of superoxide anions by alveolar macrophages may be the underlying cause of bleomycin pulmonary toxicity.
Animals↗