Vol. 166, No. 1, 1990 January 15, 1990

TUiWR SYSTEH

BIOCHEMICAL

NECROSIS FWTOR-&CRCHECTIN OF HUTWN NEUTROPHILS PHOSPHOINOSITIDES MD

Carlo

LCIUDTWNR,

Institute

of

Received

November

GWTIWTES INDEPENDENTLY THE RELECISE OF

#IRON,

Shmuel

Giorgio

Pathology,

General

29,

AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 308-315

THE Oe--GENERQTING OF THE HYDROLYSIS

fiRCICHIDONIC

BERTON

University

Filippo

and

of

OF

CICID ROSS1

Verona,

Verona,

Italy

1989

have investigated the mechanisms of transnenbrane implicated in the activation of the respiratory burst of adherent neutrophils by tumor necrosis factor-n/cachectin (TNF) . The activation of the respiratory burst by TNF is insensitive to pertussis toxin and weakly sensitive to protein kinase C inhibitors Cytochalasin I3 and dibutyryl cyclic RhP have an inhibitory effect. The activation of the respiratory burst by TNF takes place in the absence of formation of =H-inositol phosphates, 32P-phosphatidic acid, and =H-arachidonic acid. These results demonstrate that the activation of the respiratory burst by an endogenous, physiologic stimulus can be independent of the formation of messengers derived from hydrolysis of phosphoinositides. 0 1990 Academic Press, Inc. SUIIHRRY,

Ue

signalling

Tumor

necrosis

cytokine

factor-w

able

inflammatory (1).

to

modulate

reactions, is

TNF

neutrophils 1s

a

and

ion

TNF

was

a

molecules to

proteins,

they

NRDPH

of

of

(reviewed

in

activate

NRDPH

0006-291x/90 Copyright All rights

amounts

signals

oxidase

that

is ligand-receptor

are

accompanied

$1.50

0 1990 by Academic Press, Inc. of reproduction in any form reserved.

in

system

molecules,

308

different

to

indicated

that

toxic

of

(14)‘

oxygen

confirmed

when

by

neutrophils

extracellular

hydrogen

(71,

matrix

peroxide

(HrOz)

TNF.

involved

enzymatic

shown

of

to

response

as

zymosan

cells

or

the

such

response

that

serum

promotes enhances

of

Nathan

demonstrated

in

and

in

tissues

functions

of

a

involved

injured

ingestion

by

is

(2-G),

cachectin activates the O2(-)-generating system of human neutrophils independently of the hydrolysis of phosphoinositides and the release of arachidonic acid.

We have investigated the mechanisms of transmembrane signalling implicated in the activation of the respiratory burst of adherent neutrophils by tumor...
494KB Sizes 0 Downloads 0 Views