Activated Polymorphonuclear Leukocytes Rapidly Synthesize Retinoic Acid Receptor-alpha: a Mechanism for Translational Control of Transcriptional Events

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2004 Sep 1

PMID 15337793

Citations 26

Authors

Christian C Yost

Melvin M Denis

Stephan Lindemann

Frederick J Rubner

Gopal K Marathe

Michael Buerke

Thomas M McIntyre

Andrew S Weyrich

Guy A Zimmerman

Affiliations

Soon will be listed here.

Abstract

In addition to releasing preformed granular proteins, polymorphonuclear leukocytes (PMNs) synthesize chemokines and other factors under transcriptional control. Here we demonstrate that PMNs express an inducible transcriptional modulator by signal-dependent activation of specialized mechanisms that regulate messenger RNA (mRNA) translation. HL-60 myelocytic cells differentiated to surrogate PMNs respond to activation by platelet activating factor by initiating translation and with appearance of specific mRNA transcripts in polyribosomes. cDNA array analysis of the polyribosome fraction demonstrated that retinoic acid receptor (RAR)-alpha, a transcription factor that controls the expression of multiple genes, is one of the polyribosome-associated transcripts. Quiescent surrogate HL60 PMNs and primary human PMNs contain constitutive message for RAR-alpha but little or no protein. RAR-alpha protein is rapidly synthesized in response to platelet activating factor under the control of a specialized translational regulator, mammalian target of rapamycin, and is blocked by the therapeutic macrolide rapamycin, events consistent with features of the 5' untranslated region of the transcript. Newly synthesized RAR-alpha modulates production of interleukin-8. Rapid expression of a transcription factor under translational control is a previously unrecognized mechanism in human PMNs that indicates unexpected diversity in gene regulation in this critical innate immune effector cell.

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