title: Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear stress.
abstract: Local shear stresses generated by blood flow exert direct mechanical effects on adhesion of circulating leukocytes to vascular endothelium, but their effects on expression of endothelial-leukocyte adhesion molecules have not been determined. Shear stress in rabbit carotid arteries was increased by 170% or decreased by 73% in 5 days by surgical manipulations. En face immunofluorescence staining with the monoclonal antibody Rb1/9 revealed that vascular cell adhesion molecule-1 (VCAM-1) expression was greatly increased under low shear stress, but the distribution of staining was patchy. Thus, 71.4 +/- 7.8% of fields were VCAM-1 positive versus 2.4 +/- 0.47% of fields in control arteries. Frequently, large regions showed consistent but heterogeneous staining. Occasionally, small islands of cells were labeled intensely. Monocytes, detected by use of the monocyte-specific antibody HAM 56, adhered to endothelium under low shear stress; 64.5 +/- 8.2% of the monocytes colocalized with detectable VCAM-1, although many (83.2 +/- 2.8%) VCAM-1-positive regions were devoid of monocytes. VCAM-1 expression also increased significantly but to a lesser extent when shear stress was approximately doubled. Thus, 8.7 +/- 1.5% of fields were VCAM-1 positive under high shear versus 2.5 +/- 0.87% under normal shear stress. No monocytes were detected at high shear stress. At normal shear stresses, intercellular adhesion molecule-1 (ICAM-1), detected by use of the monoclonal antibody Rb2/3, was extensively distributed; thus, 53.5 +/- 5.5% of fields contained ICAM-1-positive cells. The junctional regions of the cells were heavily stained.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Max Bell Research Centre, Toronto Hospital Research Institute, Ontario, Canada.
authors.forename: P L
authors.initials: PL
authors.lastname: Walpola
authors.forename: A I
authors.initials: AI
authors.lastname: Gotlieb
authors.forename: M I
authors.initials: MI
authors.lastname: Cybulsky
authors.forename: B L
authors.initials: BL
authors.lastname: Langille
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008297:Male; D009000:Monocytes / Q000502:physiology*; D011817:Rabbits; D013314:Stress, Mechanical; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1