Delayed polymorphonuclear leukocyte infiltration is an important component of Thalassophryne maculosa venom pathogenesis.
Thalassophryne maculosa fish envenomation is characterized by severe pain, dizziness, fever, edema and necrosis. Here, the dynamic of cellular influx, activation status of phagocytic cells, and inflammatory modulator production in the acute inflammatory response to T. maculosa venom was studied using an experimental model. Leukocyte counting was performed (2 h to 21 days) after venom injection in BALB/c mice footpads. Our results showed an uncommon leukocyte migration kinetic after venom injection, with early mononuclear cell recruitment followed by elevated and delayed neutrophil influx. The pattern of chemokine expression is consistent with the delay in neutrophil recruitment to the footpad: T. maculosa venom stimulated an early production of IL-1beta, IL-6, and MCP-1, but was unable to induce an effective early TNF-alpha and KC release. Complementary to these observations, we detected a marked increase in soluble KC and TNF-alpha in footpad at 7 days post-venom injection when a prominent influx of neutrophils was also detected. In addition, we demonstrated that bone marrow-derived macrophages and dendritic cells were strongly stimulated by the venom, showing up-regulated ability to capture FITC-dextran. Thus, the reduced levels of KC and TNF-alpha in footpad of mice concomitant with a defective accumulation of neutrophils at earlier times provide an important clue to uncovering the mechanism by which T. maculosa venom regulates neutrophil movement.
Pareja-Santos
Alessandra
A
Special Laboratory of Applied Toxinology (CAT/CEPID), Butantan Institute, São Paulo, Brazil.
Oliveira Souza
Valdênia Maria
VM
Bruni
Fernanda M
FM
Sosa-Rosales
Josefina Ines
JI
Lopes-Ferreira
Mônica
M
Lima
Carla
C
D000818:Animals; D024541:Batrachoidiformes; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005397:Fish Venoms / Q000633:toxicity*; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D005397:Fish Venoms; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D015232:Dinoprostone