title: Interferon-gamma improves muscle flap microcirculation in double-strand RNA-induced inflammation.
abstract: Endothelial cell (EC) activation and subsequent expression of leukocyte adhesion molecules are initial events in multiple pathological processes. Viral double-strand ribonucleic acid (dsRNA) induces EC adhesion protein expression and leukocyte adhesion in vitro. Interferon-gamma (IFN-gamma) has been demonstrated to modulate the expression of certain adhesion proteins. The purpose of this study was to measure the inflammatory response to a viral mimetic--a synthetic dsRNA, polyinosinic-polycytidylic acid (poly-I:C)-on the microcirculation of a muscle flap in a rat model and to determine whether IFN-gamma attenuated the response. Two-stage surgery to create a cremaster muscle end-organ tube flap was performed on 18 male Sprague-Dawley rats in three groups. After intra-arterial injection into the abdominal aorta, the reagents (phosphate-buffered saline-bovine serum albumin [PBS-BSA] in groups I and II, and IFN-gamma in group III) were kept for 1 hour in this end-organ system. During the second stage at 16 hours, after injection into the penile vein (PBS-BSA in group I, poly-I:C in groups II and III), the flap was prepared for intravital microscopic measurement. The following parameters were measured: red blood cell velocity; vessel diameter; number of functional capillaries; and number of rolling, sticking, and transmigrating neutrophils and lymphocytes. Wilcoxon's rank sum test was used for statistical comparison. Poly-I:C caused a 70% increase in the main artery diameter and a 7% increase in velocity. But as a consequence of dynamic activation of leukocyte interaction, a 30% drop in functional capillary perfusion was observed. Injury to the entire vascular endothelium was confirmed by a 160% increase in transmigrating leukocytes. Treatment with IFN-gamma inhibited the poly-I:C-induced inflammation, as shown by 88%, 63%, and 85% decreases in rolling, sticking, and transmigrating leukocytes respectively, and by a 28% increase in capillary perfusion. Treating the system with IFN-gamma in advance, inhibited poly-I:C-induced inflammation, shown by marked decreases in rolling, adhering, and transmigrating leukocytes, and a notable increase in perfused capillaries. These observations reflect an inhibitory effect of IFN-gamma on leukocyte adhesion molecule expression in vascular endothelium in response to dsRNA in a muscle flap at the microcirculatory level.
authors.affiliation: Gülhane Military Medical Academy, Department of Plastic and Reconstructive Surgery, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Türegün
authors.forename: E
authors.initials: E
authors.lastname: Güdemez
authors.forename: J
authors.initials: J
authors.lastname: Zins
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: DiCorleto
authors.forename: M
authors.initials: M
authors.lastname: Siemionow
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D004730:Endothelium, Vascular / Q000378:metabolism; D007249:Inflammation / Q000503:physiopathology*; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008833:Microcirculation; D011070:Poly I-C / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps / Q000098:blood supply*
chemical_list: D007369:Interferon Inducers; D007371:Interferon-gamma; D011070:Poly I-C