HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Magazine, H. I. Articles by Stefano, G. B. Search for Related Content PubMed PubMed Citation Articles by Magazine, H. I. Articles by Stefano, G. B.

Rebound from Nitric Oxide Inhibition Triggers Enhanced Monocyte Activation and Chemotaxis¹

Harold I. Magazine^2,*,, Jungshan Chang^*, Yannick Goumon and George B. Stefano

^* Department of Biology, Queens College and the Graduate School of the City University of New York, Flushing, NY 11367; and Multidisciplinary Center for the Study of Aging, Neuroscience Research Institute, State University of New York/College at Old Westbury, Old Westbury, NY 11568

Exposure of human peripheral blood monocytes to the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) resulted in a rapid shift in cellular conformation of spontaneously activated cells from ameboid to round. The population of activated cells, 7.1 ± 1.2%, was reduced 7-fold to 1.1 ± 0.4% following 0.5 h exposure to SNAP. Observation of monocytes for 6 h demonstrated a gradual release from NO inhibition initiating at 2.5 h following SNAP treatment and a period of hyperactivity that was maximal at 5 h following SNAP exposure. During the rebound from the NO inhibition phase, there was a significant increase in the population of activated monocytes and an increased responsiveness to chemotactic agents such as IL-1, IL-8, and fMLP relative to that of cells treated with the chemotactic agents alone. Conformational changes induced by SNAP were associated with a reduction in F-actin and loss of filopodial extension. The loss and recovery of F-actin staining paralleled changes in cell activity, suggesting that NO may alter cellular activity by modulation of cytoskeletal actin. These data taken together suggest that inhibition of monocyte activity by NO results in an excitatory phase observed subsequent to release from NO inhibition and increased sensitivity to chemotactic agents. We propose that this rebound from NO inhibition may provide increased immunosurveillance to rectify immunological problems that have been encountered during the period of inhibition.