Amphotericin B causes aggregation of neutrophils and enhances pulmonary leukostasis.
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)
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects*; D004727:Endothelium / Q000166:cytology / Q000648:ultrastructure; D007962:Leukocytes / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011817:Rabbits
D000666:Amphotericin B