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J Biol Chem, Vol. 273, Issue 47, 31215-31221, November 20, 1998

Decreased Neonatal Dietary Fat Absorption and T Cell Cytotoxicity in Pancreatic Lipase-related Protein 2-Deficient Mice

Mark E. LoweDagger §, Mark H. Kaplanparallel , Laurie Jackson-GrusbyDagger Dagger , Dymphna D'AgostinoDagger , and Michael J. Grusbyparallel §§

From the Departments of Dagger  Pediatrics and § Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, the parallel  Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, the §§ Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, and Dagger Dagger  The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142

The pancreas secretes several different lipases. The most abundant is pancreatic triglyceride lipase (PTL). The pancreas also synthesizes two homologues of PTL, the pancreatic lipase-related proteins 1 and 2 (PLRP1 and PLRP2). Cytotoxic T-lymphocytes also express PLRP2 under certain conditions. We sought to determine the role of PLRP2 in fat absorption and in T-cell cytotoxicity by creating a PLRP2-deficient mouse. Adult PLRP2-deficient mice had normal fat absorption. In contrast, suckling PLRP2-deficient mice had fat malabsorption evidenced by increased fecal weight, increased fecal fats, and the presence of undigested and partially digested dietary triglycerides in the feces. As a result, the PLRP2-deficient pups had a decreased rate of weight gain. To assess T cell cytotoxicity, we immunized PLRP2-deficient mice with a mastocytoma cell line, P815, and determined the ability of splenocytes from the immunized mice to kill P815 cells in a 51Cr release assay. PLRP2-deficient cells had deficient killing activity in this assay, and PLRP2-deficient splenocytes released fewer fatty acid from the target cells than did control cells. Our results provide the first evidence of a physiological function for PLRP2. PLRP2 participates in T cell cytotoxicity, and PLRP2 performs a crucial role in the digestion of dietary fats in suckling animals.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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