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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.
Lowe §,
Mark H.
Kaplan ,
Laurie
Jackson-Grusby ,
Dymphna
D'Agostino , and
Michael J.
Grusby §§
From the Departments of Pediatrics and
§ Molecular Biology and Pharmacology, Washington University
School of Medicine, St. Louis, Missouri 63110, the 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
 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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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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