Polymorphonuclear leukocyte adhesion to articular cartilage is inhibited by cartilage surface macromolecules.
The present studies deal with polymorphonuclear neutrophil (PMN) adhesion inhibitory properties of cartilage surface proteoglycans. Normal human PMN were used in adhesion experiments with bovine cartilage surfaces exposed to neutrophil elastase and reconstituted with fibronectin (Fn) or on plastic-bound Fn. An extract of cartilage surface small proteoglycans (SE) and purified fibromodulin (FM), decorin (DCN), biglycan (BGN), and aggrecan (AGN) on the surface of normal cartilage were used to test for inhibition of Fn-dependent cell adhesion. The PMN did not adhere to intact articular cartilage surfaces, whereas significant adhesion was measured using cartilage explants digested with elastase and reconstituted with Fn. Incubation of elastase-treated, Fn-reconstituted cartilage with 45 microg/ml SE inhibited PMN adhesion by 50.7 +/- 5.8% (P < 0.0001). Addition of 50 microg/ml purified FM to the 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 microg/ml SE (20.4 +/- 8.0%). Maximal inhibition of 67.4 +/- 14.8% (P < 0.01) was obtained with 17.0 microg/ml SE. With FM, concentrations of 4.3 microg/ml resulted in 34.7 25.2 inhibition (P < 0.001), and maximal inhibition of 66.3 16.2% (P < 0.01) was obtained with 43.0 microg/ml. Similar results were obtained with purified bovine DCN and BGN. The main component of cartilage matrix, AGN, failed to inhibit cell adhesion significantly. The results indicate that macromolecules normally present on articular cartilage surfaces act as a barrier to PMN adhesion. Since cartilage surface proteins are susceptible to breakdown by proteases from synovial fluid inflammatory cells, we postulate that the degradation of this barrier may be responsible for increasing PMN adhesion and subsequent cartilage damage in inflammatory arthritis.
Mitani
Y
Y
Theresa Scheu Rheumatoid Arthritis Research Laboratory, Little Rock, AR 72205, USA.
Honda
A
A
Jasin
H E
HE
D053674:Aggrecans; D000818:Animals; D058578:Biglycan; D002352:Carrier Proteins / Q000494:pharmacology; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D058575:Decorin; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins; D000071235:Fibromodulin; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D037181:Lectins, C-Type; D019272:Leukocyte Elastase / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D011509:Proteoglycans / Q000494:pharmacology
D053674:Aggrecans; C546884:BGN protein, human; D058578:Biglycan; D002352:Carrier Proteins; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D005353:Fibronectins; D037181:Lectins, C-Type; D011509:Proteoglycans; D000071235:Fibromodulin; D019272:Leukocyte Elastase