Phalloidin prevents leukocyte emigration induced by proinflammatory stimuli in rat mesentery.
The objective of this study was to determine whether phalloidin, a potent microfilament stabilizer, can modify inflammatory mediator-induced leukocyte adhesion and extravasation in postcapillary venules of the rat mesentery. To address this issue, the rat mesentery was prepared for in vivo microscopic observation. Venules with initial diameters ranging between 25 and 35 microns were selected for study. Erythrocyte velocity, vessel diameter, leukocyte rolling velocity, and the number of adherent (stationary for 30 s) and emigrated leukocytes were initially determined during superfusion of the mesentery with phosphate-buffered saline. After these variables were recorded during the control period, either 100 nM platelet-activating factor (PAF), 20 nM leukotriene B4 (LTB4), or 1 microM N-formyl-methionyl-leucyl-phenylalanine (FMLP) was added to the superfusate. Repeat measurements were obtained between 50 and 60 min after initial exposure to the inflammatory mediator. In some experiments, rats were given phalloidin (25 or 500 micrograms/kg iv) 30 min before superfusion with the inflammatory mediators. Superfusion of the mesentery with either PAF, LTB4, or FMLP enhanced leukocyte adherence and emigration and reduced leukocyte rolling velocity. Pretreatment with the low dose of phalloidin effectively prevented leukocyte emigration but had no effect on the increased leukocyte adherence elicited by the three inflammatory mediators. However, when administered at the higher dose, phalloidin prevented both leukocyte adherence and emigration. Neither dose of phalloidin altered the upregulation of neutrophil membrane CD11/CD18 glycoprotein adherence complex induced by PAF or LTB4. These results are consistent with the concept that PAF, LTB4, and FMLP increase leukocyte extravasation by a process that may involve alterations in the endothelial cell cytoskeleton.
Asako
H
H
Department of Physiology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Wolf
R E
RE
Granger
D N
DN
Korthuis
R J
RJ
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018845:CD11 Antigens; D018821:CD18 Antigens; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005434:Flow Cytometry; D007962:Leukocytes / Q000502:physiology; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010590:Phalloidine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D014699:Venules / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D010972:Platelet Activating Factor; D010590:Phalloidine; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine