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Amphotericin-B promotes leukocyte aggregation of nylon-wool-fiber-treated polymorphonuclear leukocytes
Abstract:
Severe pulmonary reactions have been reported in patients receiving leukocyte transfusion and amphotericin-B. To study the interaction of amphotericin-B with polymorphonuclear leukocytes (PMN), purified human PMN were incubated with 200 mg of nylon wool fiber for 60 min either in the absence or presence of 2 mM EDTA. PMN were recovered in acid citrate dextrose solution and were suspended in balanced salt solution for determination of their aggregation properties. The cells exposed to nylon wool fibers without EDTA aggregated in response to concentration as low as 1.25 micrograms/ml of amphotericin-B. Cells initially treated with EDTA, however, failed to aggregate. Serum from a patient treated with amphotericin-B aggregated PMN exposed to nylon wool fiber but not control cells, whereas serum taken before amphotericin was given without effect on the PMN treated with nylon wool fiber. Amphotericin-B at 5 micrograms/ml failed to potentiate the release of beta-glucocuronidase or lactic dehydrogenase by PMN treated by nylon wool beyond that seen with exposure to the fibers alone. Rabbit peripheral blood was similarly incubated with nylon wool fibers and the recovered PMN were infused into recipient rabbits that had received 1 mg/kg of amphotericin-B intravenously 1 hr prior to the infusion of the leukocytes. Rabbits were sacrificed 30 min after transfusion of PMN, and their lungs were excised for histologic sectioning. Those rabbits receiving a combination of amphotericin-B and 4 x 10(7) nylon-wool-fiber-treated PMN had evidence of pulmonary hemorrhage and accumulation of leukocytes in the pulmonary vasculature whereas those animals who received such cells alone had normal appearing lung tissue. In summary, amphotericin-B at concentrations achievable in vivo enhanced the aggregation of PMN damaged by incubation with nylon fiber with subsequent accumulation of the phagocytes in pulmonary tissue.
Insights
Amphotericin-B can cause severe lung reactions by enhancing the aggregation of polymorphonuclear leukocytes (PMN) damaged by medical devices. This interaction leads to leukocyte accumulation in pulmonary tissues, causing hemorrhage.
Area of Science:
- Immunology
- Pharmacology
- Pulmonary Medicine
Background:
- Severe pulmonary reactions are a known risk for patients receiving leukocyte transfusions and amphotericin-B.
- The interaction between amphotericin-B and polymorphonuclear leukocytes (PMN) requires further investigation to understand these reactions.
Purpose of the Study:
- To investigate the interaction between amphotericin-B and human polymorphonuclear leukocytes (PMN).
- To determine if amphotericin-B enhances PMN aggregation and subsequent pulmonary accumulation.
Main Methods:
- Human PMN were incubated with nylon wool fibers, with or without EDTA, and then exposed to amphotericin-B.
- Aggregation properties of PMN were assessed, and in vivo studies used rabbits receiving amphotericin-B and PMN.
Main Results:
- PMN exposed to nylon wool fibers aggregated in the presence of amphotericin-B, an effect blocked by EDTA.
- Serum from patients treated with amphotericin-B induced PMN aggregation.
- In rabbits, the combination of amphotericin-B and nylon-wool-treated PMN led to pulmonary hemorrhage and leukocyte accumulation.
Conclusions:
- Amphotericin-B enhances the aggregation of PMN damaged by medical materials like nylon fiber.
- This enhanced aggregation contributes to leukocyte accumulation in pulmonary vasculature, potentially causing severe lung reactions.