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Blood, 15 April 2001, Vol. 97, No. 8, pp. 2457-2468
PHAGOCYTES
RNA expression patterns change dramatically in human
neutrophils exposed to bacteria
Yerramilli V. B. K. Subrahmanyam,
Shigeru Yamaga,
Yatindra Prashar,
Helen H. Lee,
Nancy P. Hoe,
Yuval Kluger,
Mark Gerstein,
Jon D. Goguen,
Peter E. Newburger, and
Sherman M. Weissman
From the Department of Genetics, Boyer Center for
Molecular Medicine, Yale University School of Medicine, and the
Department of Molecular Biophysics and Biochemistry, Yale University,
New Haven, CT; and the Departments of Molecular Genetics/Microbiology
and Pediatrics, University of Massachusetts Medical School, Worcester.
A comprehensive study of changes in messenger RNA (mRNA)
levels in human neutrophils following exposure to bacteria is
described. Within 2 hours there are dramatic changes in the levels of
several hundred mRNAs including those for a variety of cytokines,
receptors, apoptosis-regulating products, and membrane trafficking
regulators. In addition, there are a large number of
up-regulated mRNAs that appear to represent a common core of activation
response genes that have been identified as early-response products to
a variety of stimuli in a number of other cell types. The activation
response of neutrophils to nonpathogenic bacteria is greatly altered by exposure to Yersinia pestis, which may be a major factor
contributing to the virulence and rapid progression of plague. Several
gene clusters were created based on the patterns of gene induction caused by different bacteria. These clusters were consistent with those
found by a principal components analysis. A number of the changes could
be interpreted in terms of neutrophil physiology and the known
functions of the genes. These findings indicate that active regulation
of gene expression plays a major role in the neutrophil contribution to
the cellular inflammatory response. Interruption of these changes by
pathogens, such as Y pestis, could be responsible, at least
in part, for the failure to contain infections by highly virulent organisms.
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