No abstract

Glucan, an immunomodulator, has been reported to increase collagen deposition and tensile strength in experimental models of wound repair. Previous data suggest that glucan modulates wound healing via an indirect mechanism in which macrophages are stimulated to release growth factors and cytokines. However, recent data have shown the presence of glucan receptors on normal human dermal fibroblasts, suggesting that glucans may be able to directly stimulate fibroblast collagen biosynthesis. To test this hypothesis, we examined the effect of glucan on collagen biosynthesis in normal human dermal fibroblasts. We assessed nuclear factor‐1 (NF‐1) activation, procollagen mRNA expression, collagen biosynthesis, and whether there was a causal link between glucan treatment, NF‐1 activation, and collagen expression. Glucan (1 µg/ml) increased NF‐1 binding activity by 46% (8 hours), 64% (24 hours), 215% (36 hours), and 119% (48 hours) in cultured normal human dermal fibroblasts. Alpha 1(I) and α1 (III) procollagen mRNA were increased in glucan‐treated normal human dermal fibroblasts when compared with the untreated fibroblasts. Collagen synthesis was increased at 24 hours and 48 hours following glucan treatment of normal human dermal fibroblasts. Down‐regulation of NF‐1 by pentifylline inhibited glucan‐induced procollagen mRNA expression. These data indicate that glucan can directly stimulate human fibroblast collagen biosynthesis through an NF‐1–dependent mechanism. ( WOUND REP REG 2002;10:168)

These data indicate that anti-HLA antibodies have the ability to stimulate airway epithelial cell proliferation and that they may play an important role in the development of bronchiolitis obliterans syndrome. Prevention of HLA sensitization and immunosuppression with agents capable of blocking indirect antigen presentation and the humoral immune response against the allograft may be pivotal in preventing the development of bronchiolitis obliterans syndrome after lung transplantation.

These results indicate that anti-AEC antibodies may play a role in the immunopathogenesis of BOS in the absence of anti-HLA antibodies.