Global analysis of neutrophil gene expression

A widespread, but incorrect, view of the neutrophil portrays it as a short- lived, terminally differentiated cell that has a highly condensed nucleus a nd hence is unable to induce gene expression. However, these cells express mRNA encoding phagocytic receptors, modulate RNA synthesis in response to l ectin stimulation or glucocorticoid treatment, and upregulate genes involve d in phagocytic function, such as respiratory burst activity and cytokine s ecretion. Most studies of neutrophil gene expression have examined cytokine stimulation and have focused on a few specific genes of known interest, ra ther than the global genetic repertoire of the cell. In part stimulated by the availability of gene and expressed sequence tag databases, several appr oaches have been developed to assess the revels of all mRNA species found i n single RNA preparations. We have analyzed the regulation of gene expressi on in neutrophils using a gel-based method that displays 3' end fragments o f cDNA generated by restriction enzymes. Our data indicate that neutrophils are capable of extensive, rapid, and complex changes in gene expression, i nvolving at least several percent of all mRNAs present in the cell. The num ber and magnitude of mRNA responses are comparable to those measured on act ivation of normal T cells. The data also indicate that activated neutrophil s are a source of newly synthesized, physiologically significant, intercell ular signaling molecules. (C) 2000 Lippincott Williams & Wilkins, Inc.