Characterization of IL-1 inhibitory factor released from human alveolar macrophages as IL-1 receptor antagonist.
IL-1 possesses pleiotropic properties on various cells and its activity may be stringently regulated in several ways. We have previously reported that both IL-1 and its inhibitory factor are concomitantly released from alveolar macrophages in both healthy subjects and patients with chronic inflammatory lung diseases. An increase in IL-1 activities and a decrease in inhibitory activities are characteristics found in both healthy smokers and patients with interstitial lung diseases. In this study, we further examined the biological properties of IL-1 inhibitory factor. The inhibitor exhibited a dose-dependent specific inhibition of an augmentation by IL-1 of PHA-induced murine thymocyte proliferation, while no inhibition of the augmentation by IL-2, IL-4, IL-6, or tumour necrosis factor (TNF) was found. 125I-labelled IL-1 alpha binding on PHA-stimulated murine thymocytes revealed two types of IL-1 binding sites, 44 sites/cell with a Kd of 2.7 x 10(-10) M and 230 sites/cell with a Kd of 2.5 x 10(-9) M. Alveolar macrophage culture supernatants blocked the binding of labelled IL-1 to the IL-1 receptor in a dose-dependent fashion. Scatchard plot analysis revealed that the inhibitory factor in the supernatants blocked the binding competitively. These results indicate that alveolar macrophages produce a specific IL-1 inhibitory factor, functioning as an IL-1 receptor antagonist.
Takeuchi
M
M
Chest Disease Research Institute, Kyoto University, Japan.
Nagai
S
S
Nakada
H
H
Aung
H
H
Satake
N
N
Kaneshima
H
H
Izumi
T
T
D002478:Cells, Cultured; D002850:Chromatography, Gel; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008970:Molecular Weight; D011506:Proteins / Q000302:isolation & purification* / Q000627:therapeutic use; D012795:Sialoglycoproteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011506:Proteins; D012795:Sialoglycoproteins