Extravasation of leucocytes in tissues is mediated by leucocyte-endothelial cell interactions in which adhesion molecules play an important role. Until now, two pathways have been unravelled, i.e., the LFA-1/ICAM-1 and the VLA-4/VCAM-1 pathways. ELAM-1 has been shown to be involved in granulocyte accumulation and recently also in lymphocyte migration. The role of HECA-452 is under investigation. In this study we have investigated the expression of the above-mentioned adhesion molecules in lung tissue of patients with pulmonary sarcoidosis and usual interstitial pneumonitis (UIP), and in mediastinal lymph nodes of patients with sarcoidosis. ICAM-1 (CD54) was broadly distributed on the endothelium of all the vessels found in sarcoidosis and UIP. VCAM-1 was present on the endothelium of the venules, capillaries, and arterioles in both sarcoidosis and UIP. ELAM-1 reacted with endothelial cells lining venules and capillaries in chronic progressive sarcoidosis and in the active phase of UIP but not in the stationary phases of both diseases. HECA-452 activity could be detected only on high endothelial venules within sarcoid lymph nodes. In lung tissues, macrophages bearing the ICAM-1 antigen were present in sarcoid tissue but not in the interstitium and alveolar space of UIP. LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) were present on all leucocytes found but seemed to be more highly expressed on lymphocytes in sarcoidosis. These findings suggest that the LFA-1/ICAM-1 and VLA-4/VCAM-1 pathways are involved in leucocyte migration in both types of lung disease, while in the active phases of sarcoidosis and UIP, ELAM-1 is also involved.

way has been shown to affect lymphocyte recirculation and homing in a non-organ specific way,'2 13 whereas the VLA-4NCAM-I pathway plays an important part in lymphocyte migration into inflamed tissues.14 It has been recognised that VLA-4 not only functions as a cell receptor for VCAM-I9'1 but also as an extracellular matrix receptor for an alternatively spliced domain of fibronectin (CSI).'6-18 As in rats CS1 has been found to support the adhesion of lymphocytes to cultured peripheral lymph node (PLN)-high endothelial cells, '9 we wanted to establish whether CS1 also mediates lymphocyte-HEV interactions in humans. Expression of functional HEV binding ability was tested in a modified in vitro frozen section assay in which lymphocytes bind to HEVs of PLNs or inflamed synovial membranes. The results show that the CS1 adhesive motif of fibronectin affects physiological lymphocyte recirculation via PLN as well as lymphocyte migration to inflamed synovial tissue. Materials and methods PEPTIDESThe CS 1 peptide was used to investigate involvement of the type III connecting segment (IIICS) cell binding domain of fibronectin in lymphocyte adhesion. The adjacent peptide sequence (CS2) was used as a control. Peptides were synthesised and purified as described by Humphries et al. 8 As the maximum inhibition of T lymphocyte-HEV binding was obtained using concentrations exceeding 0 10 mg peptide/ml, a concentration of 0 15 mg/ml was used throughout the study. MONOCLONAL ANTIBODIESThe monoclonal antibodies used were CLB-45 (IgGl) specific for CD452"; HP2/1 (IgGl) and SANI (IgGl) specific for the cx chain of VLA-4 (CD49d) and VLA-5 (CD49e) respectively2' 22; 4B9 (IgGl) specific for and a rabbit polyclonal antibody against fibronectin (Dakopatts, Glostrup, Denmark).

No abstract

No abstract