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The mouse macrophage activation-associated marker protein, p71/73, is an inducible prostaglandin endoperoxide
T A Phillips1, D A Kujubu, R J MacKay
1Wilkinson Laboratory of the Cancer Center, University of Kansas Medical Center, Kansas City 66160-7184.
Abstract:
The inducible protein p71/73 marks the response of mouse macrophages to one of several stimuli (e.g., bacterial lipopolysaccharide or poly I:C) that trigger the expression of cytolytic activity when these cells have previously been primed for tumor cell killing by interferon-gamma (IFN-gamma). The results reported here identify this marker protein as the inducible prostaglandin endoperoxide synthase (PES), TIS10/PES-2. Identification was based on four findings: (1) p71/73, like the TIS10/PES-2 protein, was associated with cellular membranes; (2) the sequence of amino acids in the NH2 terminus of both p71 and p73 was 96% identical to the predicted NH2-terminal sequence of the TIS10/PES-2 protein; (3) a polyclonal antiserum raised against the COOH-terminal region of the TIS10/PES-2 gene product recognized p71/73 in immunoblots; and (4) dexamethasone, which blocks induction of TIS10/PES-2 expression, inhibited the induction of both p71/73 synthesis and tumoricidal activity in macrophage. Several regulatory roles for this protein in the activation process are possible.
Insights
The inducible protein p71/73 in mouse macrophages is identified as prostaglandin endoperoxide synthase (PES), TIS10/PES-2. This discovery links PES to macrophage activation and tumor cell killing.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Mouse macrophages, when primed by interferon-gamma (IFN-gamma), exhibit cytolytic activity against tumor cells upon stimulation.
- Specific inducible proteins, such as p71/73, are associated with this activated state.
Purpose of the Study:
- To identify the inducible protein p71/73 involved in activated macrophage responses.
- To elucidate the role of this protein in macrophage-mediated tumor cell killing.
Main Methods:
- Protein localization analysis (cellular membranes).
- Amino acid sequence comparison (NH2-terminus).
- Immunoblotting using specific antiserum against TIS10/PES-2.
- Dexamethasone treatment to assess inhibition of protein induction and activity.
Main Results:
- The inducible protein p71/73 was identified as inducible prostaglandin endoperoxide synthase (PES), also known as TIS10/PES-2.
- p71/73 shares high sequence identity with TIS10/PES-2 and localizes to cellular membranes.
- Antiserum against TIS10/PES-2 recognized p71/73.
- Dexamethasone inhibited the induction of both p71/73 and macrophage tumoricidal activity.
Conclusions:
- The inducible protein p71/73 is TIS10/PES-2, a key component in the activation of macrophages for tumor cell killing.
- PES plays a regulatory role in the macrophage activation process.
- This finding provides a molecular target for understanding and potentially modulating macrophage-mediated immunity.