LIPOPOLYSACCHARIDE INCREASES FIBRONECTIN PRODUCTION AND RELEASE FROM CULTURED LUNG FIBROBLASTS PARTIALLY THROUGH PROTEOLYTIC ACTIVITY

Fibronectin is a major product of fibroblasts and can mediate diverse functions including wound healing. Chronic bacterial infections are ge nerally associated with a marked decrease in the ability to repair. We therefore hypothesized that bacterial endotoxin, lipopolysaccharide ( LPS), might alter fibroblast fibronectin production. LPS augmented fib ronectin production by fibroblasts and also stimulated the release of fibronectin from cell layers. An increase in new protein synthesis app eared to account for part of the increased fibronectin, because the in hibitor of protein synthesis, cycloheximide, inhibited the increase in total production of fibronectin. Cycloheximide did not attenuate the increased release of fibronectin into the culture medium. This increas ed release appealed to be caused, at least in part, by fragmentation o f fibronectin by proteases contained in LPS preparations. In this rega rd all preparations of LPS tested were found to cleave fibronectin. Fi nally, zymograms indicated that LPS could also cleave gelatin with at least two bands of proteolytic activity but that it did not cleave bov ine serum albumin or ovalbumin. These results indicate that the abilit y of bacterial products to alter fibronectin production and to degrade this macromolecule may account for altered wound repair that occurs w ith chronic bacterial infection.