Departments of
* Microbiology and Infectious Diseases,
Medical Sciences, and
Internal Medicine, University of Calgary, Alberta, Canada; and
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-
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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