Polymorphonuclear leukocyte adhesion to articular cartilage is inhibited by cartilage surface macromolecules

The present studies deal with polymorphonuclear neutrophil (PMN) adhesion i nhibitory properties of cartilage surface proteoglycans. Normal human PMN w ere used in adhesion experiments with bovine cartilage surfaces exposed to neutrophil elastase and reconstituted with fibronectin (Fn) or on plastic-b ound Fn. An extract of cartilage surface small proteoglycans (SE) and purif ied fibromodulin (FM), decorin (DCN), biglycan (BGN), and aggrecan (AGN) on the surface of normal cartilage were used to test for inhibition of Fn-dep endent cell adhesion. The PMN did not adhere to intact articular cartilage surfaces, whereas significant adhesion was measured using cartilage explant s digested with elastase and reconstituted with Fn. Incubation of elastase- treated, Fn-reconstituted cartilage with 45 mug/ml SE inhibited PMN adhesio n by 50.7 +/- 5.8 % (P < 0.0001). Addition of 50 <mu>g/ml purified FM to th e reconstituted articular surfaces inhibited cell adhesion by 71.2 +/- 13.9 % (P<0.0001). Inhibition of PMN adhesion to plastic-bound Fn was seen with 1.7 <mu>g/ml SE (20.4 +/- 8.0%). Maximal inhibition of 67.4 +/- 14.8% (P<0. 01) was obtained with 17.0 <mu>g/ml SE. With FM, concentrations of 4.3 mug/ ml resulted in 34.7 +/- 25.2 inhibition (P<0.001), and maximal inhibition o f 66.3 +/- 16.2% (P < 0.01) was obtained with 43.0 mug/ml. Similar results were obtained with purified bovine DCN and BGN. The main component of carti lage matrix, AGN, failed to inhibit cell adhesion significantly. The result s indicate that macromolecules normally present on articular cartilage surf aces act as a barrier to PMN adhesion. Since cartilage surface proteins are susceptible to breakdown by proteases from synovial fluid inflammatory cel ls, we postulate that the degradation of this barrier may be responsible fo r increasing PMN adhesion and subsequent cartilage damage in inflammatory a rthritis.