Am. J. Respir. Crit. Care Med., Vol 149, No. 1, 01 1994, 191-196.
Effect of interstitial lung disease macrophages on T-cell signal transduction
JC Weissler, C Mendelson, F Moya and WC Yarbrough Jr
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235-9034.
Some types of interstitial lung disease (ILD) are characterized by an
abnormal proliferation and activation of lymphocytes in the alveolus and
interstitium. Recent data have suggested that membrane signals on alveolar
macrophages (AM) in normal lung play a crucial role in limiting 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 idiopathic
pulmonary fibrosis were compared for the ability to inhibit CD3-mediated
increases in intracellular calcium concentration [(Ca2+)i]. All normal AM
inhibited CD3-mediated increases in (Ca2+)i, whereas seven of 10 ILD AM
were permissive of this early event in T- lymphocyte activation. Patients
with ILD and permissive AM displayed significantly greater mean BAL
lymphocytes than did those with suppressive AM (42 versus 12%,
respectively). The inhibitory effect of normal AM could be partially
duplicated by incubation of lymphocytes with surfactant (SF) obtained from
normal lungs. Analysis of one SF component, SF protein A, in normal and in
ILD AM membranes disclosed reduced SF protein A in ILD AM. These results
demonstrate alterations in AM in patients with ILD and a lymphocytic
alveolitis that renders AM permissive for early events in T-cell
activation.
