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
Background— Vascular inflammatory lesions from patients with giant-cell arteritis show a remarkable amount of neovascularization, but its clinical implications have never been investigated. Methods and Results— To assess the clinical relevance of neovascularization in giant-cell arteritis, angiogenesis was measured in temporal artery sections from 31 patients with biopsy-proven giant-cell arteritis by staining endothelial cells with Ulex europaeus lectin. Angiogenesis was highly variable among these patients. Patients without ischemic complications had higher tissue angiogenesis scores than patients with ischemic events (5.69±0.6 versus 2.91±0.6, P =0.003). Angiogenesis was also more prominent in patients with a strong acute phase response (score: 5.31±0.6) compared with those with a weak systemic inflammatory reaction (2.30±0.44; P =0.0007). Serum angiogenic activity was studied in an additional series of 38 biopsy-proven patients. Sera from patients without ischemic events tended to be more active in stimulating human umbilical vein endothelial cell growth (optical density ×1000, 270±15 versus 192±14, P =0.065) and differentiation into capillary-like structures (107±5 versus 84±8 relative units, P =0.0058) than patients with ischemic complications. Sera from patients without ischemic events had more in vivo full angiogenic activity tested in the chick chorioallantoic membrane than sera from patients with ischemic complications. Conclusion— Inflammation-induced angiogenic activity may play a compensatory role for ischemia in patients with giant-cell arteritis.
To test the hypothesis of vascular sequestration of parasitized erythrocytes in Plasmodium falciparum malaria in vivo, a pathologic and immunohistochemical study was done of the microvasculature of skeletal muscle biopsy samples from P. falciparum malaria patients at different stages of severity. Parasitized red blood cells sequestered in the skeletal muscle vessels were observed in samples from necropsies but were never demonstrated in biopsy specimens. Vascular cell adhesion molecule-1 and E-selectin expression was consistent only in specimens from cerebral malaria patients. Samples from such patients had strong staining of the constitutive endothelial adhesion molecules tested. The staining intensity gradually decreased in samples from persons with milder forms of the disease. Four of 13 patients with severe malaria had aggregates of red blood cells, occasionally parasitized inside the muscle fibers. These data suggest that skeletal muscle biopsy could be a useful model for the study of the pathogenesis of malaria in vivo.
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