Magnolol inhibits Mac-1 (CD11b/CD18)-dependent neutrophil adhesion: relationship with its antioxidant effect.
Magnolol, a phenolic compound isolated from a Chinese herbal drug, Magnolia officinalis, has been shown to protect rat heart from ischemia/reperfusion injury. Neutrophil adhesion plays a crucial process during this inflammatory response. To evaluate whether magnolol prevents ischemia/reperfusion injury by inhibiting neutrophil adhesion, we determined whether magnolol can inhibit adhesion of phorbol-12-myristate-13-acetate (PMA)-activated human neutrophils to a fibrinogen-coated surface in a dose-dependent manner. Using flow cytometric analysis, we observed that magnolol pretreatment (10 min at 37 degrees C) diminished PMA (100 ng/ml)-induced Mac-1 upregulation. PMA also induced rapid intracellular accumulation of superoxide (O2-.) and hydrogen peroxide (H2O2) in neutrophils; magnolol pretreatment attenuated the accumulation of these two substances. Inhibition of reactive oxygen species by superoxide dismutase and/or catalase, which decompose O2-. and H2O2, respectively, also abolished Mac-1 upregulation and neutrophil adhesion. We conclude that magnolol inhibits neutrophil adhesion and that this can account for its anti-ischemia/reperfusion injury effect. We propose that the inhibitory effect of magnolol on neutrophil adhesion to the extracellular matrix is mediated, at least in part, by inhibition of the accumulation of reactive oxygen species, which in turn suppresses the upregulation of Mac-1 that is essential for neutrophil adhesion.
Shen
Y C
YC
Institute of Pharmacology, School of Life Science, National Yang-Ming University, Taipei, Taiwan.
Sung
Y J
YJ
Chen
C F
CF
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D005340:Fibrinogen / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017705:Lignans; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001713:Biphenyl Compounds; D017705:Lignans; D016177:Macrophage-1 Antigen; C005498:magnolol; D013481:Superoxides; D005340:Fibrinogen; D006861:Hydrogen Peroxide