EFFECTS OF PLASMA FROM HIBERNATING GROUND-SQUIRRELS ON MONOCYTE-ENDOTHELIAL CELL ADHESIVE INTERACTIONS

Adhesion and subsequent penetration of leukocytes into central nervous system ischemic tissue proceeds via a coordinated inflammatory mechan ism involving adhesion molecules at the blood-endothelium interface. M ammalian hibernation is a state of natural tolerance to severely reduc ed blood flow-oxygen delivery (i.e., ischemia). Hibernating thirteen-l ined ground squirrels were investigated in an attempt to identify fact ors responsible for regulating this tolerance. Since leukocytopenia is closely associated with entrance into hibernation, the role of leukoc yte adhesion to endothelium in this phenomenon was examined. Intercell ular adhesion molecule-1 (ICAM-1) is expressed by endothelium and regu lates interactions with circulating leukocytes that may result in marg ination or extravasation. ICAM-1 expression by rat cerebral microvascu lar endothelial cells (EC) cultured with plasma from hibernating (HP) or nonhibernating (NHP) thirteen-lined ground squirrels was dose depen dently increased by HP and, to a lesser extent, by NHP. Treatment of E C with HP coincidentally induced significantly greater increases in mo nocyte adhesion to EC (37.2%) than were observed with NHP (23.9%). Stu dy of the effects of HP and NHP on monocyte adhesion to EC may identif y mechanisms responsible for ischemic tolerance in hibernators and cou ld lead to the development of novel therapeutic approaches to the trea tment of stroke.