Involvement of beta 2-integrin in ROS-mediated neutrophil apoptosis induced by Entamoeba histolytica.
Cellular adhesion through beta 2-integrin (CD18) is an important step in signal transduction leading to apoptosis of human neutrophils, and NADPH oxidase-derived reactive oxygen species (ROS) are essential for neutrophil apoptosis induced by Entamoeba histolytica. Therefore, we investigated the role of beta 2-integrin-mediated signals in ROS-dependent neutrophil apoptosis induced by E. histolytica. Entamoeba-induced apoptosis was inhibited by pre-incubation of cells with mAb to CD18, but not CD29, suggesting that beta )-integrin plays an important role in this response. Moreover, Entamoeba-induced ROS generation in neutrophils was inhibited by mAbs against CD18 or CD11b, but not by mAbs against CD11a, CD11c, or CD29. A combination of d-galactose plus anti-CD18 mAb had a larger inhibitory effect than d-galactose alone on Entamoeba-induced apoptosis and ROS generation. Furthermore, Entamoeba-induced apoptosis and ROS generation were inhibited by pre-treatment of cells with an inhibitor of phosphatidylinositol-3-kinase (PI-3-kinase). These results indicate that beta 2-integrin and PI-3-kinase are crucial signaling molecules in ROS-dependent apoptosis of neutrophils induced by E. histolytica.
Sim
Seobo
S
Department of Environmental and Tropical Medicine, Konkuk University School of Medicine, Chungju 380-701, Republic of Korea.
Park
Soon-Jung
SJ
Yong
Tai-Soon
TS
Im
Kyung-Il
KI
Shin
Myeong Heon
MH
D000818:Animals; D017209:Apoptosis; D018821:CD18 Antigens / Q000502:physiology*; D004748:Entamoeba histolytica / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism*
D018821:CD18 Antigens; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species; D005690:Galactose