Yessotoxin inhibits phagocytic activity of macrophages.
Yessotoxin (YTX) is a sulphated polyether compound produced by some species of dinoflagellate algae, that can be accumulated in bivalve mollusks and ingested by humans upon eating contaminated shellfish. Experiments in mice have demonstrated the lethal effect of YTX after intraperitoneal injection, whereas its oral administration has only limited acute toxicity, coupled with an alteration of plasma membrane protein turnover in the colon of the animals. In vitro studies have shown that this effect is due to the inhibition of endocytosis induced by the toxin. In this work, we investigated the effects of YTX on phagocytosis by using the J774 macrophage cell line. We found that macrophages exposed to 10 or 1 nM YTX display a reduced phagocytic activity against Candida albicans; moreover, phagosome maturation is also inhibited in these cells. Such results were confirmed with resident peritoneal macrophages from normal mice. The inhibition of both phagocytosis and phagosome maturation likely involves cytoskeletal alterations, since a striking rearrangement of the F-actin organization occurs in YTX-treated J774 macrophages. Surprisingly, YTX also enhances cytokine production (TNF-alpha, MIP-1alpha and MIP-2) by J774 macrophages. Overall, our results show that low doses of YTX significantly affect both effector and secretory functions of macrophages.
Orsi
Carlotta Francesca
CF
Department of Public Health Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41100 Modena, Italy.
Colombari
Bruna
B
Callegari
Federica
F
Todaro
Antonio M
AM
Ardizzoni
Andrea
A
Rossini
Gian Paolo
GP
Blasi
Elisabetta
E
Peppoloni
Samuele
S
D000199:Actins / Q000378:metabolism; D000818:Animals; D002176:Candida albicans; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000032:analysis; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008856:Microscopy, Fluorescence; D008978:Mollusk Venoms; D035964:Oxocins / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D010588:Phagosomes / Q000737:chemistry / Q000187:drug effects
D000199:Actins; D016207:Cytokines; D008070:Lipopolysaccharides; D008978:Mollusk Venoms; D035964:Oxocins; C066632:yessotoxin