title: Activity of granzyme A, a serine protease in the killing granules of cytotoxic T lymphocytes, is reduced in cells from HIV-infected hemophiliacs.
abstract: Cytotoxic CD8+ lymphocytes (CTLs) kill virally infected target cells by releasing cytotoxic granules. The primary objective of this study was to determine whether the activity of granzyme A, a serine protease in the killing granules of CTLs is altered in HIV-infected hemophiliacs. A sensitive colorimetric assay that measures cleavage of a synthetic substrate, N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester (BLT), was used to quantitate granzyme A activity. Granzyme A activities from hemophiliacs were normalized to to granzyme A activities of healthy donors run concurrently. Granzyme A activity in CD8+ T cells from HIV-seropositive hemophiliacs was significantly lower than granzyme A activity in cells from HIV-seronegative hemophiliacs (0.48 units +/- 0.086/CD8+ T cell and 1.573 +/- 0.434 units/CD8+ T cell, respectively; p < 0.005). These results indicate that cytotoxic cells in HIV-infected hemophiliacs have reduced granzyme A activity, which may result in a defect in CTL-mediated cell killing in these patients.
authors.affiliation: Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Chiang
authors.forename: S A
authors.initials: SA
authors.lastname: Tenenbaum
authors.forename: C R
authors.initials: CR
authors.lastname: Verret
authors.forename: C A
authors.initials: CA
authors.lastname: Leissinger
authors.forename: R F
authors.initials: RF
authors.lastname: Garry
mesh_terms: D015331:Cohort Studies; D005260:Female; D053804:Granzymes; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000097:blood / Q000150:complications* / Q000201:enzymology; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000201:enzymology*; D002836:Hemophilia B / Q000097:blood / Q000150:complications / Q000201:enzymology*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D012697:Serine Endopeptidases / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology*
chemical_list: C020520:thiobenzyl benzyloxycarbonyl-L-lysinate; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; D008239:Lysine