A comprehensive study of changes in messenger RNA (mRNA) levels in human ne
utrophils following exposure to bacteria is described. Within 2 hours there
are dramatic changes in the levels of several hundred mRNAs including thos
e 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 res
ponse genes that have been identified as early-response products to a varie
ty of stimuli in a number of other cell types. The activation response of n
eutrophils to nonpathogenic bacteria is greatly altered by exposure to Yers
inia pestis, which may be a major factor contributing to the virulence and
rapid progression of plague. Several gene clusters were created based on th
e patterns of gene induction caused by different bacteria. These clusters w
ere consistent with those found by a principal components analysis. A numbe
r of the changes could be interpreted in terms of neutrophil physiology and
the known functions of the genes. These findings indicate that active regu
lation of gene expression plays a major role in the neutrophil contribution
to the cellular inflammatory response. Interruption of these changes by pa
thogens, such as Y pestis, could be responsible, at least in part, for the
failure to contain infections by highly virulent organisms. (Blood. 2001;97
:2457-2468) (C) 2001 by The American Society of Hematology.