Phalloidin attenuates postischemic neutrophil infiltration and increased microvascular permeability.
The aim of this study was to determine whether phalloidin (1 microM) or antamanide (1 microM), cyclic peptides that stabilize dense peripheral band and stress fiber F-actin in endothelium, would attenuate the increase in microvascular permeability induced by 4 h of ischemia and 30 min of reperfusion (I/R) in the isolated canine gracilis muscle. Changes in microvascular permeability (1 - sigma) were assessed by determining the solvent drag reflection coefficient for total plasma proteins (sigma) in muscles subjected to 4.5 h of continuous perfusion (nonischemic controls), I/R alone, I/R + phalloidin, or I/R + antamanide. Muscle neutrophil content was assessed by determination of myeloperoxidase (MPO) activity in tissue samples obtained at the end of the experiments. Fluorescent detection of nitrobenzoxadiazole-phallicidin in endothelial cell monolayers confirmed that phalloidin enters these cells. I/R was associated with marked increases in microvascular permeability and muscle neutrophil content (1 - sigma = 0.45 +/- 0.07; MPO = 8.9 +/- 0.5 units/g) relative to control (4.5 h continuous perfusion) preparations (1 - sigma = 0.12 +/- 0.03; MPO = 0.5 +/- 0.8 unit/g). These I/R-induced changes were largely prevented by administration of phalloidin (1 - sigma = 0.19 +/- 0.02; MPO = 0.8 +/- 0.4 U/g) or antamanide (1 - sigma = 0.07 +/- 0.11; MPO = 0.9 +/- 0.3 unit/g) at reperfusion. Similar results were obtained when phalloidin was administered before ischemia (1 - sigma = 0.24 +/- 0.04; MPO = 1.2 +/- 1.0 units/g). Although antamanide decreased superoxide production (by approximately 60%) and adherence to plastic (by approximately 75%) by activated neutrophils in vitro, phalloidin failed to alter these aspects of granulocyte function.(ABSTRACT TRUNCATED AT 250 WORDS)
Korthuis
R J
RJ
Department of Physiology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Carden
D L
DL
Kvietys
P R
PR
Shepro
D
D
Fuseler
J
J
D000199:Actins / Q000502:physiology; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D015638:Cytochalasin D / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D007511:Ischemia / Q000503:physiopathology*; D007957:Leukocyte Adherence Inhibition Test; D008297:Male; D009132:Muscles / Q000098:blood supply* / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D010590:Phalloidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D015424:Reperfusion; D013481:Superoxides
D000199:Actins; D001798:Blood Proteins; D010456:Peptides, Cyclic; D013481:Superoxides; C100265:antamanide; D010590:Phalloidine; D015638:Cytochalasin D; D009195:Peroxidase