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.
Benhaim
P
P
Department of Surgery (Wound Healing Laboratory), University of California, San Francisco 94143.
Mathes
S J
SJ
Hunt
T K
TK
Scheuenstuhl
H
H
Benz
C C
CC
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