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 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.
Lowe
M E
ME
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Lowe@Kids.wustl.edu
Kaplan
M H
MH
Jackson-Grusby
L
L
D'Agostino
D
D
Grusby
M J
MJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001824:Body Constitution; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004041:Dietary Fats / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D006579:Heterozygote; D007408:Intestinal Absorption; D008049:Lipase / Q000172:deficiency* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D010179:Pancreas / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015430:Weight Gain
D004041:Dietary Fats; D008049:Lipase; C075988:pancreatic lipase related protein 2