DECREASED NEONATAL DIETARY-FAT ABSORPTION AND T-CELL CYTOTOXICITY IN PANCREATIC LIPASE-RELATED PROTEIN 2-DEFICIENT MICE

The pancreas secretes several different Lipases. The most abundant is pancreatic triglyceride lipase (PTL). The pancreas also synthesizes tw o homologues of PTL, the pancreatic lipase-related proteins 1 and 2 (P LRP1 and PLRP2), Cytotoxic T-lymphocytes also express PLRP2 under cert ain conditions. We sought to determine the role of PLRP2 in fat absorp tion and in T-cell cytotoxicity by creating a PLRP2-deficient mouse. A dult PLRP2-deficient mice had normal fat absorption. In contrast, suck ling PLRP2-deficient mice had fat malabsorption evidenced by increased fecal weight, increased fecal fats, and the presence of undigested an d partially digested dietary triglycerides in the feces. As a result, the PLRP2-deficient pups had a decreased rate of weight gain. To asses s T cell cytotoxicity, we immunized PLRP2-deficient mice with a mastoc ytoma cell line, P815, and determined the ability of splenocytes from the immunized mice to kill P815 cells in a Cr-51 release assay. PLRP2- deficient cells had deficient killing activity in this assay, and PLRP 2-deficient splenocytes released fewer fatty acid from the target cell s than did control cells. Our results provide the first evidence of a physiological function for PLRP2, PLRP2 participates in T cell cytotox icity, and PLRP2 performs a crucial role in the digestion of dietary f ats in suckling animals.