MONOSODIUM URATE CRYSTALS PROMOTE NEUTROPHIL ADHESION VIA A CD18-INDEPENDENT AND SELECTIN-INDEPENDENT MECHANISM

The primary objective of this study was to determine whether monosodiu m urate (MSU) crystals induced neutrophil adhesion to cellular substra ta and, if so, then to elucidate the molecular mechanisms involved. Hu man umbilical vein endothelial cells, (HUVEC), as well as various othe r cellular substrata, were treated with various sized MSU crystals, wa shed, and then coincubated in the presence of neutrophils for 60 min. HUVEC exposed to MSU crystals but not to silica crystals or uric acid promoted neutrophil adhesion in a dose- and size-dependent manner, an event also observed with monolayers of rabbit synovial cells and rat i ntestinal epithelial cells. The increased neutrophil adhesion could no t be attenuated by anti-CD18, anti-intracellular adhesion molecule-1, or various anti-selectin antibodies, despite the fact that scanning el ectron microscopy revealed that neutrophils were adhering primarily to the endothelial cells rather than to exposed crystals. CD18-deficient neutrophils adhered to MSU crystal-treated HUVEC as effectively as th eir CD18-positive counterparts. The neutrophil adhesion was temperatur e dependent but did not require protein synthesis. Additionally, HUVEC phagocytosis of crystals was necessary for subsequent neutrophil-endo thelial cell interactions to transpire. Pretreatment of endothelial ce lls and neutrophils with colchicine significantly reduced the adhesive interaction. Our data demonstrate that exposure of endothelial and ot her cells to MSU crystals promotes neutrophil adhesion that occurs by a firm CD18-independent and selectin-independent adhesive mechanism.