EFFECT OF INTERSTITIAL LUNG-DISEASE MACROPHAGES ON T-CELL SIGNAL-TRANSDUCTION

Some types of interstitial lung disease (ILD) are characterized by an abnormal proliferation and activation of lymphocytes in the alveolus a nd interstitium. Recent data have suggested that membrane signals on a lveolar macrophages (AM) in normal lung play a crucial role in limitin g lymphocyte activation by altering early events in receptor-mediated signal transduction in lymphocytes. In the current study fixed AM from normal volunteers and from patients with either sarcoidosis or idiopa thic pulmonary fibrosis were compared for the ability to inhibit CD3-m ediated increases in intracellular calcium concentration [(Ca2+)i]. Al l normal AM inhibited CD3-mediated increases in (Ca2+)i, whereas seven of 10 ILD AM were permissive of this early event in T-lymphocyte acti vation. Patients with ILD and permissive AM displayed significantly gr eater mean BAL lymphocytes than did those with suppressive AM (42 vers us 12%, respectively). The inhibitory effect of normal AM could be par tially duplicated by incubation of lymphocytes with surfactant (SF) ob tained from normal lungs. Analysis of one SF component, SF protein A, in normal and in ILD AM membranes disclosed reduced SF protein A in IL D AM. These results demonstrate alterations in AM in patients with ILD and a lymphocytic alveolitis that renders AM permissive for early eve nts in T-cell activation.