Secretory Phospholipase A sub(2) Receptor-Mediated Activation of Cytosolic Phospholipase A sub(2) in Murine Bone Marrow-Derived Mast Cells
The current study examined the signal transduction steps involved in the selective release of arachidonic acid (AA) induced by the addition of secretory phospholipase A sub(2) (sPLA sub(2)) isotypes to bone marrow-derived mast cells (BMMC). Overexpression of sPLA sub(2) receptors caused a marked inc...
Saved in:
Published in | The Journal of immunology (1950) Vol. 165; no. 5; pp. 2773 - 2782 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
01.09.2000
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The current study examined the signal transduction steps involved in the selective release of arachidonic acid (AA) induced by the addition of secretory phospholipase A sub(2) (sPLA sub(2)) isotypes to bone marrow-derived mast cells (BMMC). Overexpression of sPLA sub(2) receptors caused a marked increase in AA and PGD sub(2) release after stimulation of BMMC, implicating sPLA sub(2) receptors in this process. The hypothesis that the release of AA by sPLA sub(2) involved activation of cytosolic PLA sub(2) (cPLA sub(2)) was next tested. Addition of group IB PLA sub(2) to BMMC caused a transient increase in cPLA sub(2) activity and translocation of this activity to membrane fractions. Western analyses revealed that these changes in cPLA sub(2) were accompanied by a time-dependent gel shift of cPLA sub(2) induced by phosphorylation of cPLA sub(2) at various sites. A noncatalytic ligand of the sPLA sub(2) receptor, p-amino-phenyl- alpha -D-mannopyranoside BSA, also induced an increase in cPLA sub(2) activity in BMMC. sPLA sub(2) receptor ligands induced the phosphorylation of p44/p42 mitogen-activated protein kinase. Additionally, an inhibitor of p44/p42 mitogen-activated protein kinase (PD98059) significantly inhibited sPLA sub(2)-induced cPLA sub(2) activation and AA release. sPLA sub(2) receptor ligands also increased Ras activation while an inhibitor of tyrosine phosphorylation (herhimycin) inhibited the increase in cPLA sub(2) activation and AA release. Addition of partially purified sPLA sub(2) from BMMC enhanced cPLA sub(2) activity and AA release. Similarly, overexpression of mouse groups IIA or V PLA sub(2) in BMMC induced an increase in AA release. These data suggest that sPLA sub(2) mediate the selective release of AA by binding to cell surface receptors and then inducing signal transduction events that lead to cPLA sub(2) activation. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-1 |
ISSN: | 0022-1767 |