Soluble factor(s) in rat wound fluid inhibit fibroblast populated lattice contraction

Abstract

Closure of full-thickness open wounds in loose-skinned animals is accomplished by wound contraction. Fibroblast-populated collagen lattice (FPCL) contraction is an in vitro model for studying wound contraction. Fibroblasts suspended in a collagen matrix reorient the surrounding collagen fibers, resulting in a reduction in the size of the FPCL. The organization of collagen fibers by fibroblast-generated forces produces lattice contraction. An open wound in a rat begins to show contraction by 3 days, and its size will be reduced by 50% at 7 days. Fluid from 3- and 7-day-old rat wounds was examined for its ability to affect in vitro lattice contraction. Wound fluid was found to inhibit lattice contraction. The fractions which inhibit lattice contraction had molecular weights ranging between 10,000 and 20,000, as revealed by molecular sieve chromatography, and a high positive charge, as demonstrated by ion exchange chromatography. The factor(s) was only slightly affected by added indomethacin in the FPCL contraction model. This suggests a mechanism independent of the generation of prostaglandins. The factor(s) was tested in an ATP-induced model of fibroblast contraction where it was shown to be ineffective at altering cell contraction. The factor(s) did, however, prevent cell spreading and elongation on glass surfaces. Wound fluid has a factor(s) which hinders fibroblast spreading and elongation and which inhibits FPCL contraction.