Patterns and significance of CD44 expression in lung allografts

Background: Lung allograft rejection involves the interplay of multiple cel lular populations, soluble mediators, and extracellular matrix proteins. Th e CD44 family of cell surface glycoproteins mediates a variety of cell-cell and cell-matrix interactions including lymphocyte homing to sites of antig enic challenge and fibroblast migration and invasion into extracellular mat rix, processes integral to lung allograft rejection. Methods: We performed immunohistochemical staining for CD44 on biopsies fro m allograft recipients with differing rejection experiences: Group 1 (n = 5 patients/10 biopsies) never exceeded Grade A1 or B2 acute rejection (AR); Group 2 (n =7 patients/26 biopsies) had 2 or more episodes of Grade A2 or h igher AR and no obliterative bronchiolitis (OB); Group 3 (n = 6 patients/17 biopsies) had clinical and pathologic OB. Nine infected allograft biopsies , 8 near-normal lung sections (nontransplant controls), and 13 non-transpla nt biopsies showing bronchiolitis obliterans organizing pneumonia (BOOP), o rganizing diffuse alveolar damage (DAD),; or usual interstitial pneumonia ( UIP) were also studied. Results: Allograft biopsies demonstrated significantly more CD44 staining a mong; lymphocytes, macrophages, Type II pneumocytes, and respiratory epithe lial cells than non-transplant controls, while staining of lymphocytes, mac rophages, and Type II pneumocytes did not differ significantly between: all ograft groups. Fibroblast CD44 staining in Group 3 biopsies significantly e xceeded that of controls and Groups 1 and 2, and biopsies with AR and/or OB showed more fibroblast staining than biopsies with BOOP, organizing DAD, o r UIP. Alveolar CD44-positive fibroblasts did not predict development of OB , while bronchial CD44-positive fibroblasts were followed in one case by OB . Conclusions: These findings suggest that CD44 expression is characteristic of graft-infiltrating inflammatory cells and resident; parenchymal cells, a nd may be related to the initiation and evolution of AR and OB.