Inhibition of stimulant-induced activation of phagocytic cells with tetrandrine.
Tetrandrine is an alkaloid obtained from the root of a medicinal herb which is employed in China as a treatment for silicosis. One proposed mechanism for the development of silica-induced fibrosis is lung damage resulting from particle-induced inflammation and secretion of reactive compounds from alveolar phagocytes. Therefore, the objective of the present study was to determine if tetrandrine exhibited the ability to inhibit respiratory burst activity of pulmonary phagocytes. The data indicate that although tetrandrine is not cytotoxic to phagocytic cells, it is a potent inhibitor in vitro of zymosan-stimulated oxygen consumption, superoxide anion release, and hydrogen peroxide secretion by alveolar macrophages. Tetrandrine is also effective in vivo in preventing activation of alveolar macrophages after inhalation or intratracheal instillation of silica. Tetrandrine also inhibits stimulant-induced chemiluminescence by polymorphonuclear leukocytes. Since tetrandrine does not alter stimulant-induced depolarization of phagocytic cells, its inhibitory action is not via interference with receptor-ligand binding but rather must occur elsewhere in the stimulus-secretion coupling scheme.
Castranova
V
V
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505.
Kang
J H
JH
Moore
M D
MD
Pailes
W H
WH
Frazer
D G
DG
Schwegler-Berry
D
D
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D044182:Benzylisoquinolines; D006861:Hydrogen Peroxide / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D013481:Superoxides; C009438:tetrandrine; D015054:Zymosan; D006861:Hydrogen Peroxide