MAGNOLOL INHIBITS MAC-1 (CD11B CD18)-DEPENDENT NEUTROPHIL ADHESION - RELATIONSHIP WITH ITS ANTIOXIDANT EFFECT/

Magnolol, a phenolic compound isolated from a Chinese herbal drug, Mag nolia officinalis, has been shown to protect rat heart from ischemia/r eperfusion injury. Neutrophil adhesion plays a crucial process during this inflammatory response. To evaluate whether magnolol prevents isch emia/reperfusion injury by inhibiting neutrophil adhesion, we determin ed whether magnolol can inhibit adhesion of phorbol-12-myristate-13-ac etate (PMA)-activated human neutrophils to a fibrinogen-coated surface in a dose-dependent manner. Using flow cytometric analysis, we observ ed that magnolol pretreatment (10 min at 37 degrees C) diminished PMA (100 ng/ml)-induced Mac-1 upregulation. PMA also induced rapid intrace llular accumulation of superoxide (O-2(-.)) and hydrogen peroxide (H2O 2) in neutrophils; magnolol pretreatment attenuated the accumulation o f these two substances. Inhibition of reactive oxygen species by super oxide dismutase and/or catalase, which decompose O-2(-.) and H2O2, res pectively, also abolished Mac-1 upregulation and neutrophil adhesion. We conclude that magnolol inhibits neutrophil adhesion and that this c an 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 t he accumulation of reactive oxygen species, which in turn suppresses t he upregulation of Mac-1 that is essential for neutrophil adhesion. (C ) 1998 Elsevier Science B.V.