One of the hallmarks of acute
inflammation is
neutrophil infiltration of
tissues. We investigated molecular mechanisms implicated in acute neutrophilic
inflammation induced by the
venom of a
freshwater stingray (Potamotrygon cf. henlei) in
mice. Ray
venom induced
early mobilization of
neutrophil in the
microvasculature of cremaster
mice and infiltration of the
peritoneal cavity 2 hours after
injury, in a
dose-response manner.
IL-1 beta,
IL-6,
TNF-alpha, and KC were produced. The neutrophilic infiltration did not occur in
mice with ST2 receptor and MyD88 adapters neutralized, or in those with PI3K and
p38 MAPK signaling blocked. Drastic reduction of
neutrophil infiltration to peritoneal cavities was observed in ST2(-/-), TLR2/TLR4(-/-), MyD88(-/-), TRIF-/- and
IL-17A(-/-)
mice, and a partial reduction was observed in IL-18R(-/-)
mice.
Mast cell Kit W(sh)/W(sh)-, AHR-, NLRP3-,
ICE-,
IL-1 beta-, P2RX7-, CD39-, IL-17RA-, and TBX21 KO
mice retain the
ability to induce neutrophilia in
peritoneal cavity after ray
venom injection. IL- 6 and
TNF-alpha alone were insufficient for promote neutrophilia in the absence of ST2 signaling. Finally, abundant
production of
IL-33 by
cardiomyocytes was observed. These results refine our
understanding of the importance of the
IL-33/ST2 axis and
IL-33-producing
cardiomyocytes in the early acute neutrophilia induced by
freshwater stingray
venoms.