Gene targeting was used to knockdown the expression of P-selectin by platelets a
ID: 265184 • Letter: G
Question
Gene targeting was used to knockdown the expression of P-selectin by platelets and endothelial cells in a murine breast cancer model as an experimental method to prevent metastasis of ductal carcinoma cells, which express the ligand for P-selectin. Although metastasis was diminished in these animals, the leukocyte-mediated inflammatory response to a subcutaneous soft tissue implant for breast reconstruction as well as localized tissue remodeling around the implant were substantially reduced. What is the reason for the impaired foreign body reaction to the implant in these mice?
Explanation / Answer
The P-selectins are secreted by endothelial cells and megakaryocytes. When the endothelial cells get activated during inflammation triggered by thrombin or histamine, P-selectins move ahead to the plasma membrane from the intracellular alpha granules. This initiates the aggregate formation of platelets and leucocytes in the region of injury. P-selectin plays an important role in the interaction between platelet and leucocytes.
Platelet also plays an important role in platelet-platelet binding and cellular recovery or tissue remodeling. When platelets get activated by thrombin, collagen etc., the P-selectins gets released from alpha granules and promote platelet-platelet binding, leading to fast recovery. Hence, though metastasis was diminished by gene targeting, leucocyte mediated inflammatory response and tissue remodeling will be hampered.
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