Epidermolysis bullosa dystrophica recessive fibroblasts produce increased concentrations of cAMP within a collagen matrix.

Human dermal fibroblasts grown in tissue culture can be suspended and cultured in collagen lattices. These fibroblast-populated collagen lattices (FPCL) undergo a reduction in size by the process of lattice contraction. Fibroblasts from patients with epidermolysis bullosa dystrophica recessive, EBdr, produce excessive quantities of cAMP. These high concentrations of cAMP may be related to the inability of the EBdr fibroblast to elongate and spread out when incorporated into the collagen matrix. Fibroblasts with these morphologic characteristics are not effective in contracting collagen lattices. EBdr fibroblasts in FPCL have intracellular concentrations of cAMP 8 times greater than those of normal fibroblasts in FPCL. They also have a dendritic morphology. The addition of cholera toxin or dibutyryl cAMP to normal human fibroblasts will cause elevated levels of intracellular cAMP and will inhibit the elongation and spreading of cells and lattice contraction. The cytoskeletal morphology of EBdr fibroblasts differs from that of normal human fibroblasts in FPCL. The use of rhodamine phalloidin, a specific fluorescent stain for F-actin filaments, reveals that EBdr fibroblasts show a pattern of actin distribution shared by normal fibroblasts cultured in the presence of dibutyryl cAMP or cholera toxin. It is proposed that the contractile forces responsible for lattice contraction are identical to those forces responsible for the spreading and elongation of cells. EBdr fibroblasts fail to spread and elongate within a collagen matrix and are therefore not effective in lattice contraction.