title: Phalloidin attenuates postischemic neutrophil infiltration and increased microvascular permeability.
abstract: 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)
authors.affiliation: Department of Physiology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
authors.forename: R J
authors.initials: RJ
authors.lastname: Korthuis
authors.forename: D L
authors.initials: DL
authors.lastname: Carden
authors.forename: P R
authors.initials: PR
authors.lastname: Kvietys
authors.forename: D
authors.initials: D
authors.lastname: Shepro
authors.forename: J
authors.initials: J
authors.lastname: Fuseler
mesh_terms: 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
chemical_list: D000199:Actins; D001798:Blood Proteins; D010456:Peptides, Cyclic; D013481:Superoxides; C100265:antamanide; D010590:Phalloidine; D015638:Cytochalasin D; D009195:Peroxidase