Linked Life Data

8824228

Source:http://linkedlifedata.com/resource/pubmed/id/8824228

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
1996-11-26
pubmed:abstractText
BALB/cJ mouse bone marrow-derived mast cells (BMMC) developed with interleukin (IL)-3 can be stimulated by c-kit ligand (KL) in the presence of IL-10 and IL-1beta for sequential immediate and delayed generation of prostaglandin (PG) D2 through utilization of constitutive prostaglandin endoperoxide synthase (PGHS) -1 and induced PGHS-2, respectively (Murakami, M., Matsumoto, R., Austen, K. F., and Arm, J. P. (1994) J. Biol. Chem. 269, 22269-22275). We now report that BALB/cJ BMMC stimulated with KL + IL-10 + IL-1beta also exhibit the biphasic release of [3H]arachidonic acid with an immediate phase over the first 10 min followed by a delayed phase from 2 to 7 h. The delayed phase of arachidonic acid release and of PGD2 generation was inhibited by heparin, which concomitantly released a phospholipase (PL) A2 from the cells into the supernatant. Both dexamethasone and a type II PLA2 inhibitor, 12-epi-scalaradial, suppressed delayed-phase PGD2 generation at concentrations that did not affect immediate eicosanoid generation. Transcripts for type IIA PLA2, as assessed by reverse transcription-polymerase chain reaction, were progressively induced in BALB/cJ BMMC treated for 2 to 7 h with KL + IL-10 + IL-1beta; the induction of these transcripts was down-regulated by 10(-6) M dexamethasone. The expression of steady-state transcripts and protein for cytosolic PLA2 (cPLA2) did not change. PGHS-2-dependent delayed-phase PGD2 generation elicited by IgE-dependent activation of BALB/cJ BMMC primed with KL + IL-10 was also accompanied by the induction of type IIA PLA2 transcripts and was suppressed by heparin, with concomitant release of PLA2 into the supernatant. However, both the direct, cytokine-stimulated and the cytokine-primed, IgE-dependent, delayed-phase PGD2 generation occurred in BMMC from C57BL/6J mice, which have a natural disruption of the type IIA PLA2 gene. Thus, kinetic, pharmacologic, and genetic analyses suggest that an inducible, heparin-sensitive PLA2, rather than cPLA2, provides arachidonic acid to concomitantly induced PGHS-2 for delayed-phase PGD2 biosynthesis in activated BMMC. Furthermore, this heparin-sensitive PLA2 likely represents a novel PLA2 or a new function for a known low molecular weight PLA2.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25936-44
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
A heparin-sensitive phospholipase A2 and prostaglandin endoperoxide synthase-2 are functionally linked in the delayed phase of prostaglandin D2 generation in mouse bone marrow-derived mast cells.
pubmed:affiliation
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't