Cell adhesion molecules in the development of inflammatory infiltrates in giant cell arteritis: Inflammation-induced angiogenesis as the preferential site of leukocyte-endothelial cell interactions

Abstract

JOSÉ HERNA´NDEZHERNA´HERNA´NDEZ-RODRI´GUEZRODRI´RODRI´GUEZ, JORDI ESPARZA, ALVARO URBANO-MA´RQUEZMA´MA´RQUEZ, and JOSEP M. GRAU Objective. To investigate the expression pattern of adhesion molecules involved in leukocyte-endothelial cell interactions in giant cell arteritis (GCA). Methods. Immunohistochemical analysis was performed on frozen temporal artery sections from 32 patients with biopsy-proven GCA and from 12 control patients with other diseases. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lympho-cyte function-associated antigen 1 (LFA-1), very late activation antigen 4 (VLA-4), Mac-1 (CD18/CD11b), and gp 150,95 (CD18/CD11c). Clinical and biochemical parameters of inflammation in the patients, as well as the duration of previous corticosteroid treatment, were prospectively recorded. Results. Constitutive (PECAM-1, ICAM-1, ICAM-2, and P-selectin) and inducible (E-selectin and VCAM-1) endothelial adhesion molecules for leukocytes were mainly expressed by adventitial microvessels and neovessels within inflammatory infiltrates. Concurrent analysis of leukocyte receptors indicated a preferential use of VLA-4/VCAM-1 and LFA-1/ICAM-1 at the adven-titia and Mac-1/ICAM-1 at the intima-media junction. The intensity of inducible endothelial adhesion molecule expression (E-selectin and VCAM-1) correlated with the intensity of the systemic inflammatory response. Previous corticosteroid treatment reduced, but did not completely abrogate, the expression of the inducible endothelial adhesion molecules E-selectin and VCAM-1. Conclusion. Inflammation-induced angiogenesis is the main site of leukocyte-endothelial cell interactions leading to the development of inflammatory infiltrates in GCA. The distribution of leukocyte-endothelial cell ligand pairs suggests a heterogeneity in leukocyte-endothelial cell interactions used by different functional cell subsets at distinct areas of the temporal artery. Giant cell arteritis (GCA) is a chronic granulo-matous vasculitis involving large and medium-sized arteries. About 15% of individuals suffer permanent cra-nial ischemic complications, mostly visual loss, resulting from inflammation-related vessel occlusion. Patients with GCA usually experience a dramatic symptomatic relief with corticosteroid treatment, although it has not been demonstrated that corticosteroid treatment actually influences the natural course of the disease (1,2). Both immune and genetic mechanisms seem to participate in the pathogenesis of GCA (2,3). Besides the histologic pattern showing granulomatous organiza

Elevated Production of Interleukin-6 Is Associated With a Lower Incidence of Disease-Related Ischemic Events in Patients With Giant-Cell Arteritis

“…13 Moreover, neovascularization is more remarkable in patients with a strong systemic acute-phase response 13 who, as we have also shown, are stronger producers of IL-6. 6,9 In addition to its compensatory function, angiogenesis has a proinflammatory role in large and medium-sized vessel vasculitis because newly formed vessels are the main site at which adhesion molecules for leukocytes are expressed 31 and the main sites through which leukocytes invade the vessel wall, as suggested by the transmigratory phenotype of microvessel-surrounding leukocytes. 31,32 We have shown that patients with a strong systemic inflammatory response who have elevated IL-6 production require higher and longer corticosteroid treatment.…”

“…6,9 In addition to its compensatory function, angiogenesis has a proinflammatory role in large and medium-sized vessel vasculitis because newly formed vessels are the main site at which adhesion molecules for leukocytes are expressed 31 and the main sites through which leukocytes invade the vessel wall, as suggested by the transmigratory phenotype of microvessel-surrounding leukocytes. 31,32 We have shown that patients with a strong systemic inflammatory response who have elevated IL-6 production require higher and longer corticosteroid treatment. 6,9 IL-6 -induced angiogenesis may then contribute to disease perpetuation, given the proinflammatory effects of inflammationinduced angiogenesis.…”

Contrast‐Enhanced Ultrasound of the Carotid Artery in Patients With Large Vessel Vasculitis: Correlation With Positron Emission Tomography Findings

“…Vasa vasorum ingrowth and neovascularization extension into the inner third of the media are associated with inflammation in LVV (23). Angiogenesis has a proinflammatory role in LVV because newly formed vessels are the main site at which adhesion molecules for leukocytes are expressed and the main sites through which leukocytes invade the vessel wall (24,25). Therefore, the visualization of contrast microbubbles through the thickened artery wall was construed as a potential sign of inflammation and consequently a marker of disease activity.…”

Editor's Choice – Management of Descending Thoracic Aorta Diseases

“…Concentric intimal hyperplasia is an important underlying pathologic lesion in GCA. 249 Clinical presentation varies from fever of unknown origin to constitutional symptoms. Arterial lesions may be widespread and the variable expression of GCA can be analyzed according to the anatomical pattern of the arteries affected.…”