NEUTROPHIL ADHESION TO ENDOTHELIAL-CELLS AND FACTORS AFFECTING ADHESION IN PATIENTS WITH BEHCETS-DISEASE

Objectives-To study the in vitro adhesion of polymorphonuclear leucocy tes (PMNLs) to endothelial cells in patients with Behcet's disease (ED ), and the humoral and cellular factors which may contribute to adhesi on. Methods-A total of 118 patients with ED and 60 healthy controls we re studied. In vitro adhesion of chromium-51 labelled normal neutrophi ls to human umbilical vascular endothelial cell (HUVEC) monolayers wer e studied in the presence of normal serum or serum obtained from patie nts with ED. Adhesion of neutrophils from patients with ED to HUVEC st imulated with tumour necrosis factor (TNF), interleukin-1 (IL-1), and lipopolysaccharide (LPS) and adhesion molecule (CD11a, CD11b, CD18 and L-selectin) expression on the patient's neutrophils and lymphocytes w ere determined, and the serum concentration of IL-8 was measured. Resu lts-Sera from patients with ED were found to enhance the adherence of normal PMNLs to HUVEC monolayers in vitro. Patients' sera induced an i ncrease in surface expression of CD11a and CD18 on normal neutrophils and intercellular adhesion molecule-1 (ICAM-1) expression on HUVECs. T he number of CD11a positive neutrophils was greater in the blood of pa tients with ED than in that of healthy controls (89.4% v 71%; p < 0.00 1). Pretreatment of HUVECs with IL-1 alpha, TNF alpha or LPS resulted in an increased adhesion of patients' PMNLs greater than that observed for normal PMNLs. Monoclonal antibodies to CD11a, CD11b, CD18, and IC AM-1 caused varying degrees of inhibition of neutrophil adhesion. The concentration of IL-8 was also found to be significantly increased in sera of patients with ED (490 (SD 470) pg/ml) compared with normal con trols (97.5 (56.3) pg/ml). Conclusion-Abnormalities of neutrophils, en dothelial cells, or both, have been suggested to be responsible for ma ny of the clinical manifestations of ED. Our findings may explain the underlying mechanism of neutrophil accumulation in Behcet's lesions.