Abstract
Clostridium perfringens causes gas gangrene with inflammatory myopathies and infrequently septicemia associated with massive intravascular hemolysis. The microorganism is known to produce a variety of toxins and enzymes that are responsible for severe myonecrotic lesions. Notably, alpha-toxin, which possesses hemolytic, necrotic and lethal activities, and phospholipase C and sphingomyelinase activities, is an important agent for the diseases. The cytokine storm induced by alpha-toxin, mainly the release of TNF-alpha, plays an important role in the death and massive hemolysis. The toxin-induced release of TNF-alpha from neutrophils and macrophages is dependent on the activation of ERK1/2 signal transduction via TrkA receptor. In addition, 14- and 15-membered macrolides specifically block the toxin-induced events through the activation of neutrophils and macrophages.
MeSH terms
-
Animals
-
Anti-Bacterial Agents / pharmacology
-
Anti-Bacterial Agents / therapeutic use
-
Bacterial Toxins* / adverse effects
-
Bacterial Toxins* / pharmacology
-
Calcium-Binding Proteins* / adverse effects
-
Calcium-Binding Proteins* / pharmacology
-
Clostridium perfringens / pathogenicity*
-
Gas Gangrene / drug therapy
-
Gas Gangrene / microbiology*
-
Hemolysis
-
Humans
-
MAP Kinase Signaling System / physiology
-
Macrolides / pharmacology
-
Macrolides / therapeutic use
-
Macrophages / metabolism
-
Neutrophils / metabolism
-
Phosphorylation / drug effects
-
Receptor, trkA / physiology
-
Tumor Necrosis Factor-alpha / metabolism
-
Type C Phospholipases* / adverse effects
-
Type C Phospholipases* / pharmacology
Substances
-
Anti-Bacterial Agents
-
Bacterial Toxins
-
Calcium-Binding Proteins
-
Macrolides
-
Tumor Necrosis Factor-alpha
-
Receptor, trkA
-
Type C Phospholipases
-
alpha toxin, Clostridium perfringens