PMID- 2834374
OWN - NLM
STAT- MEDLINE
DCOM- 19880606
LR  - 20210219
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 263
IP  - 13
DP  - 1988 May 5
TI  - Changes in diacylglycerol labeling, cell shape, and protein phosphorylation 
      distinguish "triggering" from "activation" of human neutrophils.
PG  - 6322-8
AB  - Upon activation neutrophils release reactive oxygen intermediates such as 
      superoxide anion (O2-) which are potent mediators of inflammation. Various agents 
      elicit different responses; N-formylmethionylleucylphenylalanine (fMLP) (0.1 
      microM) provokes brisk generation of superoxide anion; leukotriene B4 (LTB4, 0.1 
      microM) is a poor stimulus. In contrast, phorbol myristate acetate (PMA, 1.6 
      microM) acting directly via protein kinase C is a potent stimulus for O2-. We 
      compared the kinetics of appearance of various "second messengers" with the 
      capacity of these ligands to elicit O2- generation. Kinetic analysis showed a 
      two-phase response to membrane ligands; both an "early" (less than or equal to 15 
      s) and a "late" (greater than 15 s) increase in [3H]- and [14C]diacylglycerol 
      (DG) was noted in response to fMLP. In contrast, LTB4 elicited only a rapid early 
      increase in DG. The rise in DG evoked by PMA was late. Cytochalasin B increased 
      the late phase of DG labeling elicited by all agonists. Moreover, comparison of 
      increases in [3H]DG versus those of [14C]DG at early and late time points 
      suggested that DG was not formed exclusively from the hydrolysis of 
      polyphosphoinositides. Early increments of DG were also accompanied by addition 
      of plasma membrane (ultrastructural morphometry); the ratio of surface perimeter 
      to area increased rapidly (10 s) and persisted (60 s) in response to fMLP. 
      Increments were more gradual in response to PMA. Kinetic analysis of protein 
      phosphorylation was compared to the early and late increments of DG labeling. A 
      47,000 Mr protein was phosphorylated with kinetics consistent with the production 
      of O2- and DG in response to fMLP (early and late) and PMA (late). In contrast, 
      LTB4 provoked only early phosphorylation of this protein. The temporal pattern of 
      the formation of diacylglycerol and the phosphorylation of proteins describe a 
      dual signal. The data suggest that neutrophils require not only "triggering" (the 
      rapid generation of a signal) but also "activation" (the maintenance of a signal) 
      to sustain responses.
FAU - Reibman, J
AU  - Reibman J
AD  - Department of Medicine, New York University Medical Center, New York 10016.
FAU - Korchak, H M
AU  - Korchak HM
FAU - Vosshall, L B
AU  - Vosshall LB
FAU - Haines, K A
AU  - Haines KA
FAU - Rich, A M
AU  - Rich AM
FAU - Weissmann, G
AU  - Weissmann G
LA  - eng
GR  - AI18676-05/AI/NIAID NIH HHS/United States
GR  - AM 11949/AM/NIADDK NIH HHS/United States
GR  - HL 19721/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Diglycerides)
RN  - 0 (Glycerides)
RN  - 0 (Proteins)
RN  - 11062-77-4 (Superoxides)
RN  - 1HGW4DR56D (Leukotriene B4)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Diglycerides/*metabolism
MH  - Glycerides/*metabolism
MH  - Humans
MH  - Kinetics
MH  - Leukotriene B4/pharmacology
MH  - Molecular Weight
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Proteins/*metabolism
MH  - Superoxides/metabolism
MH  - Time Factors
EDAT- 1988/05/05 00:00
MHDA- 1988/05/05 00:01
CRDT- 1988/05/05 00:00
PHST- 1988/05/05 00:00 [pubmed]
PHST- 1988/05/05 00:01 [medline]
PHST- 1988/05/05 00:00 [entrez]
AID - S0021-9258(18)68789-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1988 May 5;263(13):6322-8.