PMID- 6358353
OWN - NLM
STAT- MEDLINE
DCOM- 19840107
LR  - 20081121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 131
IP  - 6
DP  - 1983 Dec
TI  - Studies on the mechanism of the human natural killer cell lethal hit: evidence 
      for transfer of protease-sensitive structures requisite for target cell lysis.
PG  - 2710-3
AB  - These studies analyze the effects of various enzymes on the terminal, killer 
      cell-independent (KCIL) stages of the human natural killer (NK) cytolytic 
      mechanism. The addition of trypsin (T), chymotrypsin (CT), or papain (P) to 
      standard NK reaction mixtures (PBL or LGL and K562 cells) completely ablated 
      cytolytic activity, whereas collagenase was ineffective. Inhibition by T was 
      reversed by preincubation with soybean trypsin inhibitor (SBTI) or fetal calf 
      serum, indicating that the inhibition was indeed due to T. Kinetic analysis with 
      the Ca++ pulse experiment indicated that T, CT, and P inhibited lysis well beyond 
      the Ca++-dependent (EDTA-sensitive) stages and essentially stopped further 51Cr 
      release at the time of addition. This observation was confirmed by the ability of 
      T, CT, and P to block lysis during KCIL of programmed K562 targets that were 
      detached from NK cells by EDTA and were suspended in dextran-containing media. 
      The lysis of K562 cells by natural killer cell-derived cytotoxic factors (NKCF) 
      was also blocked by T and CT but not by P. Inhibition of NKCF activity by T could 
      be reversed by SBTI or fetal calf serum. The ability of T, CT, or P to inhibit 
      the lysis of "programmed" K562 targets during KCIL indicates that the NK lethal 
      hit is an active process mediated by protease-sensitive structures, possibly 
      NKCF, delivered to the target cell by the NK cell during the Ca++-dependent 
      programming steps.
FAU - Hiserodt, J C
AU  - Hiserodt JC
FAU - Britvan, L J
AU  - Britvan LJ
FAU - Targan, S R
AU  - Targan SR
LA  - eng
GR  - AI-15332/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Lymphotoxin-alpha)
RN  - 0 (Trypsin Inhibitors)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.21.1 (Chymotrypsin)
RN  - EC 3.4.21.4 (Trypsin)
RN  - EC 3.4.22.2 (Papain)
SB  - IM
MH  - Binding, Competitive
MH  - Blood Physiological Phenomena
MH  - Chymotrypsin/pharmacology
MH  - Cytotoxicity, Immunologic/*drug effects
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Lymphotoxin-alpha/metabolism/*pharmacology
MH  - Papain/pharmacology
MH  - Peptide Hydrolases/*pharmacology
MH  - Trypsin/pharmacology
MH  - Trypsin Inhibitors/pharmacology
EDAT- 1983/12/01 00:00
MHDA- 1983/12/01 00:01
CRDT- 1983/12/01 00:00
PHST- 1983/12/01 00:00 [pubmed]
PHST- 1983/12/01 00:01 [medline]
PHST- 1983/12/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1983 Dec;131(6):2710-3.