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PMID: 6930649 Published · ppublish English Journal Article

A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 77 ·No. 5 ·1980-05-00 ·Pages 2533-6

Hirata F, Schiffmann E, Venkatasubramanian K, Salomon D, Axelrod J

Abstract

When rabbit peritoneal neutrophils were treated with glucocorticoids, their chemotactic response to stimulation by the chemoattractant fMet-Leu-Phe was markedly reduced. Preincubation of cells with glucocorticoids also decreased phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) activity in situ as measured by the release of [1-14C]arachidonic acid previously incorporated into phospholipids. The inhibitory potencies of glucocorticoids on phospholipase A2 activity correlated well with their anti-inflammatory activities and their abilities to bind to glucocorticoid receptors. Inhibitors of RNA and protein synthesis suppressed the inhibitory effect of glucocorticoids on phospholipase A2 activity. Digestion of the glucocorticoid-treated cells by Pronase overcame the inhibitory activity. Phospholipase A2 activity induced by Ca2+ ionophore A23187 was not affected by Pronase treatment. Gel filtration of proteins from neutrophil membranes labeled with [3H]lysine showed an induction of protein(s) (about 40,000 daltons) after glucocorticoid treatment. This protein inhibited a partially purified pancreatic phospholipase A2 and reduced the peptide-initiated chemotactic response of neutrophils.

MeSH Terms
Animals Arachidonic Acids/metabolism Chemotaxis, Leukocyte/drug effects Enzyme Inhibitors/biosynthesis Glucocorticoids/pharmacology Inflammation/physiopathology Neutrophils/drug effects,enzymology Phospholipases/antagonists & inhibitors Phospholipases A/antagonists & inhibitors Phospholipases A2 Phospholipids/metabolism RNA, Messenger/metabolism Rabbits Structure-Activity Relationship
Chemicals
Arachidonic Acids Enzyme Inhibitors Glucocorticoids Phospholipids RNA, Messenger Phospholipases Phospholipases A Phospholipases A2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hirata F
Schiffmann E
Venkatasubramanian K
Salomon D
Axelrod J
References (15)
15 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.77.5.2533
Published
1980-05-00
Pages
2533-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC349435
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.77.5.2533 PMC Full Text View journal details
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