Transendothelial movement of liposomes in vitro mediated by cancer cells, neutrophils or histamine.
A two-chamber culture system has been used to examine the ability of small liposomes to cross an endothelial cell barrier in response to various stimuli. Transendothelial transit of liposomes was almost negligible in the presence of intact, healthy endothelial cells (EC). Addition of histamine induced a concentration-dependent increase in the movement of liposomes across the EC monolayer. In the presence of polymorphonuclear neutrophils (PMNs), migrating in response to a chemotactic gradient of N-Formil-Met-Leu-Phe (fMLP), both liposomes and IgG crossed EC monolayer by a paracellular pathway, largely independent of an association with the PMNs. The presence of cancer cell, growing in the lower chamber or the presence of cancer cell-conditioned media, also resulted in the passage of liposome across the EC. We conclude that EC monolayers are sufficiently disrupted by several physiologically relevant stimuli to allow for the transendothelial passage of liposomes. These results have important implications for the therapeutic use of liposome in the treatment of cancer or other inflammatory processes.
Institute of Cellular Biology and Pathology N. Simionescu, Bucharest, Romania.
Felicia
F
Antohe
Lei
L
Lin
Grace Y
GY
Kao
Mark J
MJ
Poznansky
Theresa M
TM
Allen
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D003110:Colonic Neoplasms / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008081:Liposomes; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D024042:Collagen Type I; D017077:Culture Media, Conditioned; D007074:Immunoglobulin G; D008081:Liposomes; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine