Are intraepithelial lymphocytes in celiac mucosa responsible for inducing programmed cell death (apoptosis) in enterocytes? Histochemical demonstration of perforins in cytoplasmic granules of intraepithelial lymphocytes.
BACKGROUND
Programmed cell death refers to the genetically determined processes by which cells die in response to physiologic extracellular and intracellular signals, morphologically described as apoptosis. In physiologic and pathologic circumstances this process may involve effector and target cells.


METHODS
To identify serine esterase granules in intraepithelial lymphocytes, fresh-frozen human small intestine mucosal sections from normal and celiac-affected mucosa were incubated with substrate-specific N-alpha-benzyloxy-carbonyl-L-lysine thiobenzyl (BLT) and a chromogen (4 Benzoylamino-2,5-diethoxybenzene-dazonium chloride hemi [zinc chloride] salt as capture agent and were examined by light microscopy.


RESULTS
Normal mucosa showed an occasional intraepithelial lymphocyte with BLT-positive intracytoplasmic granules. Some large mononuclear cells of the lamina propria were similarly stained. Many more intraepithelial lymphocytes were BLT-positive among the surface enterocytes of untreated celiac mucosa. Lamina propria mononuclear cells close to the basal layer of crypt cells also appeared to be increased.


CONCLUSIONS
The histochemical identification of BLT-positive esters within intraepithelial lymphocytes suggests their involvement in enterocyte death under physiologic conditions. The increased BLT-positive intraepithelial lymphocytes found in the celiac mucosa may be related to the known increase in cytotoxic intraepithelial lymphocytes in untreated celiac disease.
Department of Pediatrics, Assaf Harofe Medical Center, Sackler Medical School, Tel-Aviv University, Israel.
M
M
Shiner
M
M
Eran
S
S
Freier
J
J
Faber
D
D
Branski
D017209:Apoptosis; D002446:Celiac Disease / Q000473:pathology*; D002648:Child; D003594:Cytoplasmic Granules / Q000737:chemistry*; D053804:Granzymes; D006651:Histocytochemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008214:Lymphocytes / Q000502:physiology / Q000648:ultrastructure*; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000032:analysis
D008562:Membrane Glycoproteins; C115996:N-benzyloxy-carbonyl-lysine thiobenzyl; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; D008239:Lysine