Activation of human granulocyte type 1-prophospholipase A2.

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Activation of human granulocyte type 1-prophospholipase A2. Abstract Text:

D Rae,N Beechey-Newman,L Burditt,N Sumar,J Hermon-Taylor,

Using an assay for measurement of released type 1-prophospholipase A2 (type 1-proPLA2) propeptides (PROP assay), we have shown that human granulocytes, but not lymphocytes or macrophages, abundantly express this 'pancreatic' type 1-proPLA2 zymogen. Stimulation with tumour necrosis factor-alpha (TNF-alpha) and other cytokines results in the immediate release from granulocytes of a mixture of free propeptides and type 1-proPLA2 precursor. We also found that granulocytes contain an approximately 29 kDa trypsin-like endogenous type 1-proPLA2 activator. PROP assay and TAP (trypsinogen activation peptide) assay of plasma samples accurately predicts the segregation of acute pancreatitis into three clearly defined categories of severity--mild, intermediate and severe--at the time of first hospital admission and over the next few hours of observation. Mild and intermediate pancreatitis are associated with a degree of granulocyte stimulation limited to the release of the unactivated type 1-proPLA2 precursor. Progression to severe disease is accompanied by the activation of granulocyte type 1-proPLA2, apparently carried to completion. This identifies the approximately 29 kDa endogenous activator of type 1-proPLA2 in granulocytes as a critical mediator at a threshold stage in acute pancreatitis, which marks the transition from uncomplicated pancreatitis to the potentially lethal disease. Specific inhibitors of this key regulatory enzyme modelled on the P3-P1 domain of the type 1-proPLA2 activation peptide would seem to be promising candidates for a new class of chemotherapeutic agents.

Activation of human granulocyte type 1-prophospholipase A2. Publishing Authors By Initials

D Rae,N Beechey-Newman,L Burditt,N Sumar,J Hermon-Taylor,

For similar peptides: protein sorting signals research abstracts see: peptides: protein sorting signals research

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Activation of human granulocyte type 1-prophospholipase A2. Journal Published:

PUBLICATION TYPE: Review

Journal: Scandinavian journal of gastroenterology. Suppleme

VOLUME: 219

Page Numbers: 24-7

Journal Abbreviation: Scand. J. Gastroenterol. Suppl

ISSN: 0085-5928

DAY: 13

MONTH: 02

YEAR: 1996

Activation of human granulocyte type 1-prophospholipase A2. Information

Number of References: 20

LANGUAGE: eng

NlmUniqueID: 437034

Activation of human granulocyte type 1-prophospholipase A2. Keywords Mesh Terms:

KEYWORDS: Protein Sorting Signals

MESH TERMS: metabolism

Chemical & Substance for Abstract: Activation of human granulocyte type 1-prophospholipase A2. Information

Substance Name: prophospholipase A2

Registry Number: EC 3.1.1.4

Grant and Affiliation Information for Activation of human granulocyte type 1-prophospholipase A2.

AFFILIATION: Dept. of Surgery, St George's Hospital Medical School, London, UK.

Country: NORWAY

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MEDLINETA: Scand J Gastroenterol Suppl

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