Effects of a factor derived from polymorphonuclear leukocytes on the growth and collagen metabolism in normal and scleroderma skin fibroblast cultures

Effects of a factor (15 kDa) derived from polymorphonuclear leukocytes (PMNs) on the growth and collagen metabolism of normal and scleroderma skin fibroblasts in culture were investigated. Skin fibroblasts from papillary, reticular or whole dermis of 5 patients with scleroderma and 7 normal controls were cultured in the presence or absence of PMN factor. The factor affected skin fibroblasts, (i) to stimulate cell proliferation, (ii) to stimulate collagenase production as observed by its functional activity, but (iii) to suppress collagen production with little effect on collagen types at a stage before the translational level. Scleroderma fibroblasts were less susceptible to the factor than normal fibroblasts in terms of cell proliferation and protein synthesis including collagen. Stimulation of cell proliferation by the factor was higher with reticular cells than papillary cells, while stimulation of collagenase production was inversely high in papillary cells and little stimulation was noted with reticular cells. Suppression of collagen production was also eminent in papillary cells, compared with that in reticular cells. These results suggest that PMNs function at the inflammatory stage in shifting tissue metabolism to a catabolic phase by releasing a factor which stimulates connective tissue cells, and that decreased susceptibility of scleroderma cells and reticular cells to PMN factor may provide for a positive factor in the accumulation of collagen in the reticular dermis of scleroderma skin.