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Amphotericin B causes aggregation of neutrophils and enhances pulmonary leukostasis
Abstract:
The influence of amphotericin B (AmB) on the aggregation of polymorphonuclear leukocytes (PMN) was examined by means of in vitro aggregometry as well as in an in vivo model of pulmonary leukostasis (PL). The AmB caused a dose-dependent aggregation of PMN that was partially blocked by addition of serum to the drug prior to its reaction with the PMN. No aggregation of PMN was seen after the addition of nystatin, a similar polyene antibiotic. In vivo studies were conducted in rabbits, where PL was induced by an intravenous infusion of zymosan-activated plasma (ZAP) or phorbol myristate acetate (PMA), and the degree of resulting leukostasis was expressed as the number of PMN per high power field (HPF). Animals in the control group had 6 +/- 3 PMN/HPF. This number increased to 12.4 +/- 5.6 when ZAP was infused and postmortem examination was performed 1 h later and to 17.4 +/- 4 if the examination was performed after 24 h. These numbers increased more than twice when AmB (1 mg/kg) was infused together with the ZAP. Increased PL after the infusion of ZAP and AmB was not attenuated by prior administration of methylprednisolone (30 mg/kg) to the animals. Infusions of AmB per se caused no significant PL but did cause increased pinocytosis in the pulmonary endothelium. Enhancement of PL by AmB was also examined in a model of PMA-induced PL.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Amphotericin B (AmB) significantly increases polymorphonuclear leukocyte (PMN) aggregation and pulmonary leukostasis (PL) in vivo. This effect, dose-dependent and not blocked by methylprednisolone, highlights AmB
Area of Science:
- Immunology
- Pharmacology
- Pulmonary Medicine
Background:
- Polymorphonuclear leukocytes (PMN) play a critical role in inflammatory responses.
- Pulmonary leukostasis (PL) is a condition characterized by the accumulation of leukocytes in the lungs.
- Amphotericin B (AmB) is an antifungal medication with known side effects.
Purpose of the Study:
- To investigate the effect of Amphotericin B (AmB) on polymorphonuclear leukocyte (PMN) aggregation.
- To evaluate the influence of AmB on in vivo pulmonary leukostasis (PL).
Main Methods:
- In vitro aggregometry was used to assess PMN aggregation induced by AmB.
- An in vivo model of pulmonary leukostasis was established in rabbits using zymosan-activated plasma (ZAP) or phorbol myristate acetate (PMA).
- The degree of PL was quantified by counting PMN per high power field (HPF).
Main Results:
- AmB induced a dose-dependent aggregation of PMN in vitro, partially inhibited by serum.
- In vivo, AmB administration significantly increased PL in rabbits challenged with ZAP or PMA.
- Methylprednisolone did not attenuate the AmB-induced enhancement of PL.
- AmB alone did not cause significant PL but increased pinocytosis in pulmonary endothelium.
Conclusions:
- Amphotericin B promotes PMN aggregation and exacerbates pulmonary leukostasis.
- The findings suggest a direct pro-inflammatory effect of AmB on leukocytes and pulmonary vasculature.
- Further research is warranted to understand the mechanisms and clinical implications of AmB-induced PL.