Induction of neutrophil Mac-1 integrin expression and superoxide production by the medicinal plant extract gossypol.
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.
Department of Surgery (Wound Healing Laboratory), University of California, San Francisco 94143.
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Benhaim
S J
SJ
Mathes
T K
TK
Hunt
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Scheuenstuhl
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Benz
D000470:Alkaloids / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004492:Edetic Acid / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006072:Gossypol / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D015394:Molecular Structure; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D016897:Respiratory Burst / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004492:Edetic Acid; D013482:Superoxide Dismutase; D011493:Protein Kinase C; D019311:Staurosporine; D006072:Gossypol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium