Expression of insulin-like growth factor-I (IGF-I) in alveolar macrophages and lymphocytes obtained by bronchoalveolar lavage (BAL) in interstitial lung diseases (ILD). Assessment of IGF-I as a potential local mitogen and antiapoptotic cytokine.
Little is known about IGF-I expression in the alveolar lymphocytes (AL), and about local role of IGF-I in physiological conditions and in interstitial lung diseases. Bronchoalveolar lavage was carried out in patients with silicosis, asbestosis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis, as well as in control subjects (n = 13, 9, 12, 56, 15, resp). Alveolar macrophages (AM) and lymphocytes (AL) were studied for (1) IGF-I, BCL-2, Fas and Fas Ligand expression and (2) cell cycle (incl. sub-G1 peak of late apoptosis) with propidium iodide (PI). Flow cytometry (FC) and immunocytochemistry were used. AL early apoptosis was detected by Annexin V FITC/PI staining. IGF-I was present in AL of all tested groups. The number of IGF-I positive AL was significantly higher in IPF (52 +/- 6.7%) and in later (II and III) stages of sarcoidosis (39 +/- 7.8 vs 16 +/- 4.0% in controls, p < 0.05). Increased BCL-2 expression in AL was detected in IPF and sarcoidosis. In all tested groups, AL were almost exclusively Fas+ T cells. Generally, a low number of AL entered apoptosis; no significant differences were found between patient groups, except decreased apoptosis rate in sarcoidosis (0.60 +/- 0.17 vs 1.15 +/- 0.33% in controls, p < 0.05). Proportion of AL positive for IGF-I was significantly correlated with parameters reflecting AL and AM cell proliferation and BCL-2 expression (e.g. AL IGF-I+ vs AM in S phase of cell cycle: r(S) = +0.50, p = 0.001), but not with apoptosis. The results show that human alveolar lymphocytes express IGF-I in normal conditions, as well as in ILD. The proportion of IGF-I+ lymphocytes was significantly increased in IPF and at later stages of sarcoidosis. In our material there was no evidence for profibrogenic or antiapoptotic activity of IGF-I. We suggest that IGF-I originating from AL may be locally active as a mitogen for alveolar macrophages and lymphocytes in ILD.
Kopiński
Piotr
P
Chair Gene Therapy, Collegium Medicum, Nicolaus Copernicus University, M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland. mpkopins@consoft.com.pl
Sładek
Krzysztof
K
Szczeklik
Jerzy
J
Soja
Jerzy
J
Szlubowski
Artur
A
Balicka-Slusarczyk
Barbara
B
Lackowska
Bozena
B
Plato
Marta
M
Szpechciński
Adam
A
D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D017563:Lung Diseases, Interstitial / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008934:Mitogens / Q000096:biosynthesis*
D008934:Mitogens; D007334:Insulin-Like Growth Factor I