The immunologic relationship of human neutrophil and skin collagenases

An understanding of the immunologic relationships between collagenases of various cellular origins is necessary to define the roles of various cell types in the pathologic tissue destruction seen in chronic inflammatory diseases, such as rheumatoid arthritis. We compared the immunologic cross-reactivity of human neutrophil and skin fibroblast collagenases, utilizing polyclonal antisera prepared to purified enzymes. Polyclonal antisera from rabbits immunized with neutrophil collagenase recognized fibroblast collagenase, as well as the neutrophil enzyme, when analyzed by immunoblot techniques. The cross-reactive epitopes constituted a major proportion of the antibody population, as shown by competitive inhibition enzyme-linked immunosorbent assay; 50% of the antibody to neutrophil collagenase was inhibited by skin collagenase. Paradoxically, antisera to fibroblast collagenase failed to recognize the neutrophil enzyme, either by immunoblot techniques or competitive inhibition enzyme-linked immunosorbent assay, an observation which supports the notion that there are unique immunodominant epitopes. The cross-reactivity with skin fibroblast collagenase shown by the neutrophil antibody suggests a conservation of epitopes between collagenases of different cellular origins. The presence of epitopes unique for each enzyme, however, could lead to a feasible approach for investigating the differential contribution of various cell types to collagenolytic activity in inflamed tissues.