The continuing studies presented here examine the role of monocytes (MO) derived from both hyper-tensive and normotensive rats in interactions with cerebral microvascular endothelial cells (EC) and their potential role as critical components in vascular disorders such as stroke. Adhesion of resting MO from SHR and WKY rats to untreated cultures of syngeneic cerebral microvascular EC were not significantly different. Activation of MO by culture with LPS or IL-1 beta and TNF-alpha up- regulated Mac-1 expression on SHR MO to a greater degree than was observed with WKY MO. Treatment of SHR MO resulted in a greater up- regulation of adhesion to both syngeneic and allogeneic EC than was observed with WKY MO. The degree of up-regulated adhesion to SHR EC monolayers was greater than was observed for WKY EC. Binding of untreated and activated MO to untreated EC monolayers could be partially inhibited (40-55% and 65-75%, respectively) by antibodies against beta2 integrins and ICAM-1. No inhibition was observed with antibodies to VLA-4. The binding of both resting and activated MO to stimulated EC was less inhibited (20-39%) by antibodies to beta2 integrins and ICAM-1; MO adhesion to stimulated EC was also partially inhibited (10%) by antibody to VLA-4. No differences in the percent inhibition by antibody treatment were observed between SHR and WKY MO cultures. The experiments presented here examine the contribution of hypertension to pathogenic mechanisms involving vascular endothelium. The findings demonstrate that MO adhesion to EC utilized beta2-integrins/ICAM-1 as well as other molecules. The findings also indicate the significantly higher adhesiveness expressed by MO from hypertensive rats as compared to normotensive rats. These studies suggest that hypertension enhances responsiveness of MO to inflammatory factors that promote adhesion. Subsequent MO interaction with endothelium via cytokines may be important in the genesis of stroke and may and contribute to pathological changes seen in stroke and reperfusion injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002865-05
Application #
2579629
Study Section
Special Emphasis Panel ( SB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code