In Vitro Effects Of Hyperbaric Oxygen On Rat Splenic Lymphocytes And The Mechanism

After exposure to hyperbaric oxygen (HBO), rat splenic lymphocytes in vitro produce more ROS (Reactive Oxygen Species). Now, ROS, especially H2O2, is regarded as signaling molecule and necessary for lymphocyte functions. Exogenous ROS, such as H2O2, can induce T cell entry into the cell cycle; however, excess of oxidative stress may lead to decrease T cell activation, leading to anergy or tolerance. Exposure of almost all kinds of cultured cells to massive amounts oxidants results in a strong accumulation of phosphate on protein tyrosine residues. Protein tyrosine phosphorylation is regulated by opposite action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) and represents a key event in the signaling cascade. Many evidences suggest that PTPs, rather than PTKs, are a direct target for oxidant species in mammalian cells. These enzymes are especially prone to inactivation by oxidation of a critical cysteine residue located in their catalytic site. As one would expect, some tyrosine phosphatases exert mainly inhibitory functions, by decreasing both the intensity and the duration of antigen receptor signals and by setting thresholds for activation of immune cells. This is in fact the case for the cytosolic tyrosine phosphateses SHP-1. However, CD45, an enzyme very abundant at T cell membrane, has been convincingly shown to facilitate the activation cascade initiated by antigen receptors and especially to be required for Ca2+ entry in response to receptor activation.So, we assume that there was inconsistency between ROS as"endogenous signaling molecules and mild oxidative stress promoting lymphocyte cell functions"and"excess of oxidative stress impairing signaling pathway". This may be due to the complexity reactions between ROS and PTPs. We presume that changes of lymphocyte functions after exposure to HBO result from the shift of PTPs activities by excessive ROS and changes of protein tyrosine phosphorylation cascade, and finally influence T cell activation signaling pathway.