Microcystins -LA, -YR, and -LR action on neutrophil migration.
Microcystins (MCs) produced by some freshwater cyanobacterial species possess potent liver toxicity as evidenced by acute neutrophil infiltration. Here, we investigate the ability of three structurally distinct toxins (MC-LA, MC-LR, and MC-YR) to evoke neutrophil recruitment per se and their effects on migration pathways. Intravital microscopic studies showed that topical application of only MC-LR enhanced the numbers of rolling and adhered leukocytes in the endothelium of postcapillary mesenteric venules. The latter effects may be dependent upon induction of the synthesis and expression of L-selectin and beta2-integrin in neutrophils, as assessed by flow cytometry and RT-PCR, respectively. Conversely, the three toxins promoted direct locomotion of neutrophils and enhanced their migration in response to fMLP, as measured by Boyden chamber assays, and increased intracellular calcium, a messenger in the chemotaxic process. In conclusion, our results show that MCs act on specific pathways of neutrophil recruitment, indicating their potential effect on neutrophils activation.
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Prof. Lineu Prestes, 580 bloco 13 B, 05508-900 Butanta, São Paulo, SP, Brazil.
Paula
P
Kujbida
Elaine
E
Hatanaka
Marco Aurélio Ramirez
MA
Vinolo
Kaline
K
Waismam
Danielle Maia de Holanda
DM
Cavalcanti
Rui
R
Curi
Sandra Helena Poliselli
SH
Farsky
Ernani
E
Pinto
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D036904:Leukocyte Rolling; D008297:Male; D008387:Marine Toxins; D052998:Microcystins / Q000494:pharmacology*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
D008387:Marine Toxins; D052998:Microcystins; C065685:microcystin YR; C049865:cyanoginosin-LA; C057862:cyanoginosin LR; D002118:Calcium