The recruitment of p47(phox) and Rac2G12V at the phagosome is transient and phosphatidylserine dependent.

Background Information: During phagocytosis, neutrophils internalise pathogens in a phagosome and produce reactive oxygen species (ROS) by the NADPH oxidase to kill the pathogen. The cytosolic NADPH oxidase subunits p40(phox), p47(phox), p67(phox) and Rac2 translocate to the phagosomal membrane to participate in enzyme activation. The kinetics of this recruitment and the underlying signalling pathways are only partially understood.

Amiloride derivatives modulate PS externalization in neutrophil-like PLB-985 cells.

During brain or cardiac ischemia/reperfusion neutrophils are recruited and activated contributing to inflammation and tissue damage. Neutrophils are removed from inflamed tissues by phosphatidylserine-dependent phagocytosis. Production of reactive oxygen species by the neutrophil NADPH-oxidase is known to affect phosphatidylserine externalization.

Involvement of the Na+/H+ exchanger in membrane phosphatidylserine exposure during human platelet activation.

Platelet membrane phosphatidylserine (PS) exposure that regulates the production of thrombin represents an important link between platelet activation and the coagulation cascade. Here, we have evaluated the involvement of the Na+/H+ exchanger (NHE) in this process in human platelets. PS exposure induced in human platelets by thrombin, TRAP, collagen or TRAP+ collagen was abolished in a Na+ -free medium.

Signaling pathways involved in glucocorticoid-induced apoptosis of thymocytes.

This review synthesizes recent insights on the signaling pathways triggered by glucocorticoids during apoptosis of thymocytes. Thymocyte apoptosis is a complex process, which is involved in thymic selection. Even if the main partners are identified, there still remain dark zones on the whole pathway and notably on the crosstalk between each signaling cascade.

Sphingosine contributes to glucocorticoid-induced apoptosis of thymocytes independently of the mitochondrial pathway.

During the selection process in the thymus, most thymocytes are eliminated by apoptosis through signaling via TCR or glucocorticoids. The involvement of ceramide (Cer) and sphingosine (SP), important apoptotic mediators, remains poorly defined in glucocorticoid-induced apoptosis. We report that, in mouse thymocytes, apoptosis triggered by 10(-6) M dexamethasone (DX) was preceded by a caspase-dependent Cer and SP generation, together with activation of acidic and neutral ceramidases.

Involvement of sodium in early phosphatidylserine exposure and phospholipid scrambling induced by P2X7 purinoceptor activation in thymocytes.

Extracellular ATP (ATP(ec)), a possible effector in thymocyte selection, induces thymocyte death via purinoceptor activation. We show that ATP(ec) induced cell death by apoptosis, rather than lysis, and early phosphatidylserine (PS) exposure and phospholipid scrambling in a limited thymocyte population (35-40%). PS externalization resulted from the activation of the cationic channel P2X7 (formerly P2Z) receptor and was triggered in all thymocyte subsets although to different proportions in each one.

Involvement of sphingosine in dexamethasone-induced thymocyte apoptosis.

It is generally accepted that ceramide plays an essential role in apoptosis. In this study we suggest that in thymocytes, dexamethasone-induced apoptosis is mediated by sphingosine rather than ceramide, through the activation of an aSMase and a cerase in a caspase-dependent manner.

Extracellular ATP induces phosphatidylserine externalization earlier than nuclear apoptotic events in thymocytes.

The present study shows for the first time that ATP(ec) induces a very early PS exposure in thymocytes and that this process can be induced in the absence of Ca(2+) influx and caspase activation.