CD44 AND HYALURONAN EXPRESSION IN HUMAN CUTANEOUS SCAR FIBROBLASTS

Fibrotic disorders of skin and other organs are typically associated w ith an abnormal accumulation of extracellular matrix. This study focus es on a matrix constituent, hyaluronan-which is known to be altered in fibrotic disorders of skin- and on CD44, a cell adhesion molecule and putative receptor for hyaluronan. Tissue samples were obtained from b iopsies of human normal skin, normal cutaneous scar, and hypertrophic cutaneous scar. After culturing, cells were studied by single- and dou ble-labeling immunohistochemistry using the two anti-CD44 monoclonal a ntibodies, BU-52 and J173, and a biotinylated hyaluronan binding compl ex probe, b-HABR. Certain cultures were Pretreated with Streptomyces h yaluronidase to assess the dependency of CD44 expression on the presen ce of endogenous hyaluronan. CD44 expression, both in the presence and the absence of exogenous hyaluronan was quantitated by radioimmunobin ding assay. Overall glycosaminoglycan synthesis and identification of hyaluronan were accomplished by precursor incorporation assays and by quantitative cellulose acetate electrophoresis. CD44 was found to be a normal human adult fibroblastic antigen whose expression is markedly increased for hypertrophic scar fibroblasts compared with normal skin fibroblasts. Although hyaluronan was found to be the predominant glyco saminoglycan constituent of the pericellular matrix for these fibrobla sts, CD44 attachment to the cell surface is neither mediated by hyalur onan nor is the presence of hyaluronan a prerequisite for CD44 express ion. Exogenous hyaluronan induced a decline in measurable CD44 express ion for normal skin fibroblasts but not for hypertrophic scar fibrobla sts. These observations are compatible with current understanding of t he way cells manage the hyaluronan economy of the extracellular matrix and emphasize phenotypic heterogeneities between fibroblasts derived from normal versus scar tissues.