Antibody-dependent tumour cytolysis by human neutrophils: effect of synthetic serine esterase inhibitors and substrates.
The requirement for serine esterase activity in antibody-dependent cellular cytotoxicity (ADCC) in human neutrophils against Raji target cells has been investigated. The lysis was prevented when the serine esterase inhibitors TPCK and TLCK (chloromethyl-ketone derivatives of tosylamino acids) were introduced into the system. Moreover, neutrophils pretreated with TPCK or TLCK and washed were inhibited as well, via a process unaffected by the presence of adequate amounts of enzymatic substrates. This suggests that the inhibition mediated by TPCK and TLCK is independent of serine esterase blockade, therefore implying the inactivation of some other step crucial to the lysis. The addition of synthetic chymotrypsin substrates (tyrosine and phenylalanine esters) impaired the Raji cell lysis in a dose-related manner without altering the constitution of neutrophil-target conjugates. Trypsin ester substrates were ineffective. These results are in agreement with the involvement of a serine esterase activity with chymotrypsin-like specificity, which should participate in the lysis at a post-binding step. We conclude that neutrophil-mediated ADCC, as developed in our model system, needs the intervention of a serine esterase or esterases, like other systems of cell-mediated cytotoxicity.
Dallegri
F
F
First Medical Clinic, University of Genova Medical School, Italy.
Frumento
G
G
Ballestrero
A
A
Goretti
R
R
Torresin
A
A
Patrone
F
F
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D004950:Esterases / Q000037:antagonists & inhibitors*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology
D014107:Tosyllysine Chloromethyl Ketone; D014108:Tosylphenylalanyl Chloromethyl Ketone; D004950:Esterases; C022635:serine esterase