IL-8 release and neutrophil activation by Clostridium difficile toxin-exposed human monocytes

The American Journal of Physiology
J K LinevskyC P Kelly

Abstract

Neutrophil infiltration is central to the pathogenesis of Clostridium difficile toxin A-induced enterocolitis. This study examines whether monocyte activation by C. difficile toxins is instrumental in initiating neutrophil activation and recruitment. Human monocytes were exposed to low concentrations of highly purified C. difficile toxins, and the conditioned media were harvested for cytokine and functional assays. Monocytes exposed to C. difficile toxin A (10(-10) M) or toxin B (10(-12) M) released 100 and 20 times basal levels, respectively, of the neutrophil chemoattractant interleukin-8 (IL-8). Reverse transcriptase-polymerase chain reaction demonstrated a marked increase in IL-8 mRNA expression by monocytes 3 h after toxin exposure. Conditioned media from toxin A- and toxin B-treated monocytes stimulated neutrophil migration (324 and 245% of control, respectively). This effect was completely blocked by IL-8 antiserum. These media also upregulated neutrophil CD11b/CD18 and endothelial cell intercellular adhesion molecule-1 expression. C. difficile toxins, at low concentrations, potently activate monocytes to release factors, including IL-8, that facilitate neutrophil extravasation and tissue infiltration. Our findings indic...Continue Reading

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Citations

May 7, 2009·FEMS Microbiology Letters·Peter I DuncanIrène Corthésy-Theulaz
Feb 14, 2003·American Journal of Physiology. Cell Physiology·Dezheng ZhaoCharalabos Pothoulakis
May 28, 2020·MBio·Mayuresh M AbhyankarWilliam A Petri
Jul 13, 2006·FEMS Immunology and Medical Microbiology·Anna WanahitaDaniel M Musher
Oct 14, 2008·Gastroenterology·Xinhua ChenCiarán P Kelly

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