Effects of 8-aminoquinolines on the ultrastructural morphology of Pneumocystis carinii

M. P. Goheen, M. S. Bartlett, M. M. Shaw, Sherry Queener, J. W. Smith

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Primaquine and other 8-aminoquinolines are effective against Pneumocystis carinii in culture and animal models but the way(s) in which they affect P. carinii are not known. This study used transmission electron microscopy to observe early effects of 8-aminoquinolines on P. carinii grown with human embryonic lung fibroblasts in microcarrier suspension culture. The 8-aminoquinolines evaluated were primaquine and Walter Reed Army Institute for Research (WR) compounds WR6026, WR238605 and WR242511. Samples of P. carinii were taken at 0, 3, 6, 12, 24 and 48 hours from culture flasks containing selected concentrations of the drugs. Time matched samples from a parallel culture without drug served as controls. All the 8-aminoquinolines produced similar morphologic alterations of the internal structure of P. carinii. Initially, dilatation of the nuclear envelopes and membranous arrays arising from the reticular system were observed. Later, more organisms displayed large arrays of smooth membranous material often presenting a concentric membranous pattern. Subsequently, cellular organization was lost resulting in necrosis. At concentrations tested WR242511 appeared to be the most effective, producing alterations in many trophozoites after 6 hours of exposure; WR6026 appeared to be the least effective with some organisms unaffected after 48 hours. The changes observed are consistent with damage to the reticular system of P. carinii, which might be caused by oxidation by the 8-aminoquinolines or their metabolites.

Original languageEnglish
Pages (from-to)379-387
Number of pages9
JournalInternational Journal of Experimental Pathology
Volume74
Issue number4
StatePublished - 1993

Fingerprint

Pneumocystis carinii
Primaquine
Trophozoites
Nuclear Envelope
8-aminoquinoline
Transmission Electron Microscopy
Pharmaceutical Preparations
Dilatation
Suspensions
Necrosis
Animal Models
Fibroblasts
Lung

Keywords

  • 8-aminoquinoline
  • Pneumocystis carinii
  • transmission electron microscopy
  • ultrastructure

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Effects of 8-aminoquinolines on the ultrastructural morphology of Pneumocystis carinii. / Goheen, M. P.; Bartlett, M. S.; Shaw, M. M.; Queener, Sherry; Smith, J. W.

In: International Journal of Experimental Pathology, Vol. 74, No. 4, 1993, p. 379-387.

Research output: Contribution to journalArticle

Goheen, M. P. ; Bartlett, M. S. ; Shaw, M. M. ; Queener, Sherry ; Smith, J. W. / Effects of 8-aminoquinolines on the ultrastructural morphology of Pneumocystis carinii. In: International Journal of Experimental Pathology. 1993 ; Vol. 74, No. 4. pp. 379-387.
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