Elevation of oleate-activated phospholipase D activity during thymic atrophy

Area of Science:

• Biochemistry
• Immunology
• Cell Biology

Background:

• Phospholipases are implicated in thymocyte apoptosis in vitro.
• The in vivo role of phospholipase D (PLD) in thymic atrophy is not well understood.

Purpose of the Study:

• To investigate the in vivo activity of phospholipase D (PLD) in rat thymus following X-irradiation or dexamethasone (DEX) administration.
• To determine the cellular localization and functional significance of PLD during thymic atrophy.

Main Methods:

• Rats were subjected to whole-body X-irradiation or injected with dexamethasone (DEX).
• Exogenous [14C]dipalmitoyl phosphatidylcholine (PC) was used to measure PLD activity.
• Thymocytes and stromal cells were isolated for differential PLD activity assessment.
• In vitro phagocytosis assays using P388D1 cells and PLD inhibitors were performed.

Main Results:

• Oleate-activated PLD activity significantly increased in the thymus during atrophy, peaking at sevenfold after irradiation and fourfold after DEX injection.
• Elevated levels of phosphatidic acid (PA), a PLD product, were detected, originating from PC.
• The major increase in PLD activity was observed in isolated stromal cells, not thymocytes.
• PLD activation occurred during in vitro phagocytosis of apoptotic thymocytes, and this process was inhibited by PLD blockers.

Conclusions:

• Increased phospholipase D (PLD) activity is an in vivo event during thymic atrophy.
• PLD plays a role in the phagocytic clearance of apoptotic thymocytes by stromal cells.
• Alterations in PLD activity are associated with thymus shrinkage induced by irradiation or DEX.