Abstract
Gossypol is present in antiinflammatory poultices made from the medicinal tree Thespesia populnea. Isolated human neutrophils exposed to 3-20 microM gossypol for 15-90 min were assayed in vitro for superoxide production and surface expression of Mac-1 (CD11b/CD18). Gossypol increased superoxide production in a time- and concentration-dependent fashion consistent with a moderate, delayed respiratory burst. Surface Mac-1 expression was increased within 15 min by 3-5 microM gossypol, resulting in a 14-fold increase over controls and a threefold greater increase over that produced by PMA. Staurosporine failed to block gossypol induction of superoxide and Mac-1, while EDTA inhibited induction of Mac-1 only, implicating a calcium-dependent mechanism. Gossypol increased intracellular calcium to peak levels, but in a delayed fashion as compared to FMLP. These findings demonstrate that gossypol is a highly potent stimulant of Mac-1 expression and suggest at least two protein kinase C-independent pathways of neutrophil activation. The resultant exhaustion of neutrophils may account for the antiinflammatory properties of plants containing gossypol.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Alkaloids / pharmacology
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
-
Calcium / metabolism
-
Cells, Cultured
-
Edetic Acid / pharmacology
-
Enzyme Induction / drug effects
-
Gene Expression Regulation / drug effects*
-
Gossypol / chemistry
-
Gossypol / pharmacology*
-
Humans
-
Intracellular Fluid / metabolism
-
Macrophage-1 Antigen / biosynthesis*
-
Macrophage-1 Antigen / genetics
-
Molecular Structure
-
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
-
Neutrophils / drug effects*
-
Neutrophils / metabolism
-
Oxidative Phosphorylation / drug effects
-
Protein Kinase C / antagonists & inhibitors
-
Respiratory Burst / drug effects*
-
Signal Transduction / drug effects
-
Staurosporine
-
Stereoisomerism
-
Structure-Activity Relationship
-
Superoxide Dismutase / biosynthesis*
-
Superoxide Dismutase / genetics
-
Tetradecanoylphorbol Acetate / pharmacology
-
Up-Regulation / drug effects
Substances
-
Alkaloids
-
Anti-Inflammatory Agents, Non-Steroidal
-
Macrophage-1 Antigen
-
N-Formylmethionine Leucyl-Phenylalanine
-
Edetic Acid
-
Superoxide Dismutase
-
Protein Kinase C
-
Staurosporine
-
Gossypol
-
Tetradecanoylphorbol Acetate
-
Calcium