Endothelial functional responses and increased vascular permeability induced by polycations.
Polycations such as poly-L-lysine powerfully stimulated cultured endothelial cells from pig aorta to release prostacyclin and cytoplasmic purines in a dose (charge)-dependent and molecular weight (size) dependent manner. Neutral or anionic polymers were inactive. Qualitatively similar findings were made in vivo where poly-L-lysine induced charge and size-dependent local edema formation after intradermal injection in the rabbit. Pretreatment of cultured endothelium with heparin or trypsin (but not neuraminidase) effectively reduced the response of the cells to subsequent exposure to poly-L-lysine suggesting an interaction of polycations with integral membrane proteins. Edema responses to poly-L-lysine were reduced in the presence of indomethacin suggesting that generation of an endogenous vasodilator prostaglandin, perhaps endothelial cell-derived, was an important component of the response. Poly-L-lysine-induced edema formation was not dependent on endogenous histamine release but was reduced by locally administered trasylol while soybean trypsin inhibitor failed to inhibit the response. Our results indicate that polycations such as poly-L-lysine can induce responses of vascular endothelium in vitro and in vivo and that the effects are not only charge-related but are also dependent on the size of the polycation. We suggest that naturally occurring polycations such as those derived from leukocytes and platelets may play an important role in various pathologic processes and that this may be closely related to their size.
Needham
L
L
Section of Vascular Biology, MRC Clinical Research Centre, Harrow, Middlesex, United Kingdom.
Hellewell
P G
PG
Williams
T J
TJ
Gordon
J L
JL
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D007611:Aprotinin / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006493:Heparin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008863:Microspheres; D008970:Molecular Weight; D011107:Polylysine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms; D013552:Swine; D014357:Trypsin / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011687:Purines; D011720:Pyrazoles; D011107:Polylysine; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D006493:Heparin; D007611:Aprotinin; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D014357:Trypsin; D011738:Pyrilamine