Interleukin-2 alters the positions of capillary and venule pericytes in rat cremaster muscle.
Interleukin-2 (IL-2) mediates regression of metastatic cancer, but its therapeutic efficacy has been limited by toxicities which occur secondarily to IL-2 induced macromolecular leakage from microvessels. Previous studies have indicated that pericytes function in an endothelial cell junction-dependent manner in lung capillaries and cremaster muscle venules, possibly to limit cellular and macromolecular leakage. The purpose of this investigation was to determine if pericyte positioning on skeletal muscle capillaries was junction-related, and if it was altered by IL-2. Anesthetized rats received intravenous injections of fluoroscein isothiocyanate conjugated to albumin. The cremaster muscle model of microcirculation was used in conjunction with intravital fluorescence microscopy to monitor changes in interstitial fluorescence which was used as an index of macromolecular leakage. IL-2 induced a progressive increase in interstitial albumin which started within 30 min of application and continued to increase until the end of the experiment at two hours. Cremaster muscle tissue was fixed and prepared for examination by transmission electron microscopy. A digitizing platter and morphometric software were used to quantify pericytes near vs away from endothelial cell junctions of capillaries and venules. In microvessels from animals in the control group, pericytes were randomly positioned on capillaries, and concentrated at endothelial cell junctions of venules. After treatment with IL-2, capillary pericytes were concentrated at junctions. Venular pericyte density also increased in endothelial junctional regions. IL-2 appears to alter the distribution of pericytes in the microcirculation, perhaps by induction of contraction.
Sims
D E
DE
Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
Miller
F N
FN
Horne
M M
MM
Edwards
M J
MJ
D000818:Animals; D002196:Capillaries / Q000166:cytology* / Q000187:drug effects; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000098:blood supply; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000166:cytology* / Q000187:drug effects
D005456:Fluorescent Dyes; D007376:Interleukin-2