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 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.
Weissler
J C
JC
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235-9034.
Mendelson
C
C
Moya
F
F
Yarbrough
W C
WC
D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000032:analysis; D016022:Case-Control Studies; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D011510:Proteolipids / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis; D017565:Sarcoidosis, Pulmonary / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D002118:Calcium