Clostridium difficile toxin A alters in vitro-adherent neutrophil morphology and function.
The effects of purified toxin A in vitro on the shape and function of polymorphonuclear leukocytes (PMNL) were examined. Toxin A induced changes in adherent PMNL shape from a compact spherical or pyramidal shape to a thin and rope-like shape. This change in shape was accompanied by rearrangement of the F-actin cytoskeleton into aggregates. Toxin A-treated PMNL exhibited increased adherence and expressed less L-selectin and more Mac-1, compared with untreated PMNL. In contrast to these proinflammatory actions, toxin A impaired both directed and non-directed PMNL migration in response to N-formylmethionylleucylphenylalanine. In addition, toxin A decreased the oxidative activity of adherent PMNL stimulated by recombinant human tumor necrosis factor-alpha. These effects could be explained by toxin A-induced glucosylation of the signaling small-size guanine 5'-triphosphate-binding proteins of the Rho family in human PMNL.
Brito
Gerly A C
GA
Department of Morphology, Federal University of Ceará, Fortaleza, Brazil
Sullivan
Gail W
GW
Ciesla
William P
WP
Carper
Holliday T
HT
Mandell
Gerald L
GL
Guerrant
Richard L
RL
D001427:Bacterial Toxins / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000633:toxicity*; D006031:Glycosylation; D006801:Humans; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008855:Microscopy, Electron, Scanning; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D001427:Bacterial Toxins; D004768:Enterotoxins; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; C041348:tcdA protein, Clostridium difficile; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D020741:rho GTP-Binding Proteins