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Effects of Clostridium difficile toxin B on human monocytes and macrophages: possible relationship with cytoskeletal rearrangement.
- Source :
-
Infection and immunity [Infect Immun] 1993 Mar; Vol. 61 (3), pp. 1082-90. - Publication Year :
- 1993
-
Abstract
- Toxin B from Clostridium difficile is cytopathic in vitro for various types of cells, including polymorphonuclear cells, lymphocytes, and monocytes. Since intestine lamina propria is rich in macrophages, we studied the effect of toxin B on human monocytes and on human macrophages generated in vitro by long-term culture of purified circulating blood monocytes. Upon addition of toxin B, human monocytes exhibited few modifications whereas macrophages adopted a stellate morphology, with rounding up of the perikaryon. Toxin B made microfilaments of actin disappear and induced an important reorganization of vimentin and a redistribution of tubulin. Membrane area increased by approximately 16%. Toxin B did not affect the viability of human mononuclear phagocytes and did not exert any significant lytic effect. It profoundly altered the phagocytic function of macrophages. When activated by gamma interferon in the presence of toxin B, monocytes were more cytotoxic for U-937 target cells than control monocytes activated in absence of toxin. Finally, the combined treatment of monocytes with gamma interferon and toxin B increased significantly the secretion of tumor necrosis factor alpha, whereas toxin B alone was unable to induce tumor necrosis factor production. These results suggest that morphological and functional alterations induced in human mononuclear phagocytes by toxin B from C. difficile are due to the disorganization of the cytoskeleton and the resulting impairment of the membrane traffic equilibrium.
- Subjects :
- Cell Differentiation drug effects
Cell Division drug effects
Cell Membrane drug effects
Cell Membrane ultrastructure
Cell Survival drug effects
Cytoskeleton drug effects
Enterocolitis, Pseudomembranous etiology
Enterocolitis, Pseudomembranous pathology
Humans
In Vitro Techniques
Interferon-gamma metabolism
Macrophage Activation
Macrophages physiology
Macrophages ultrastructure
Monocytes physiology
Monocytes ultrastructure
Phagocytosis drug effects
Tumor Necrosis Factor-alpha metabolism
Bacterial Proteins
Bacterial Toxins pharmacology
Cytoskeleton ultrastructure
Macrophages drug effects
Monocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0019-9567
- Volume :
- 61
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 8432590
- Full Text :
- https://doi.org/10.1128/iai.61.3.1082-1090.1993