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(Journal of Leukocyte Biology. 2002;71:458-468.)
© 2002 by Society for Leukocyte Biology

Distinct fates of monocytes and T cells directly activated by Pseudomonas aeruginosa exoenzyme S

Slava Epelman*, Graham G. Neely2, Ling Ling Ma2, Mark Gjomarkaj3, Elisabetta Pace3, Mario Melis3, Donald E. Woods* and Christopher H. Mody*

Departments of
* Microbiology and Infectious Diseases,
{dagger} Medical Sciences, and
§ Internal Medicine, University of Calgary, Alberta, Canada; and
{ddagger} Istituto di Fisiopatologia Respiratoria, CNR, Palermo, Italy

Correspondence: Christopher H. Mody, M.D., FRCPC, Rm. 273, Heritage Medical Research Building, 3330 Hospital Dr., N.W., University of Calgary, Calgary, Alberta, Canada, T2N-4N1. E-mail: cmody{at}ucalgary.ca

Gram-negative infections can cause overwhelming inflammatory responses. Although factors other than LPS are clearly involved, these factors and their mechanisms of action have been poorly defined. During studies of LPS-independent inflammatory responses of the gram-negative pathogen Pseudomonas aeruginosa, an important virulence factor (exoenzyme S) was shown to be a potent mitogen for T cells. The current work demonstrates that exoenzyme S selectively induced transcription and secretion of biologically active cytokines and chemokines (chemotactic for neutrophils and T cells) from monocytes. Exoenzyme S stimulated highly purified monocytes independent of T cells. In addition, exoenzyme S stimulated T cells directly; neither T-cell activation (CD69) nor apoptosis (hypodiploidy) required the presence of monocytes. However, T-cell activation was enhanced via a noncontact-dependent mechanism as a result of the secretion of TNF-{alpha} and IL-6. This study identifies a unique property of a gram-negative-derived microbial product capable of activating multiple cell types and suggests a mechanism by which exoenzyme S contributes to the immunopathogenesis of cystic fibrosis and sepsis in patients infected with P. aeruginosa.

Key Words: gram negative • inflammation • apoptosis • mitogen




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