Human alveolar macrophages produce predominantly the 35-kD pro-forms of interleukin-1 alpha and interleukin-1 beta when stimulated with lipopolysaccharide.
Alveolar macrophages (AM) play a key role in local immunoregulation. The objective of these studies was to compare the production of the pro- and mature forms of both interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) by AM from nine nonsmoking control subjects, six asymptomatic smokers, and nine patients with interstitial lung disease (ILD). IL-1 alpha and IL-1 beta steady-state mRNA levels in AM cultured over 20 h were determined using specific cDNA probes. IL-1 alpha, 35-kD pro-IL-1 beta, and 17-kD mature IL-1 beta protein levels in cell lysates and supernatants were determined by individual specific ELISAs. Before culture, the isolated AM contained no IL-1 alpha or IL-1 beta mRNA. AM from nonsmoking control subjects and asymptomatic smokers produced comparable levels of IL-1 alpha protein, 5.01 +/- 1.02 ng/ml and 4.54 +/- 1.07 ng/ml, respectively, only after stimulation with lipopolysaccharide (LPS) and not with granulocyte-macrophage colony-stimulating factor (GM-CSF). The majority of the IL-1 alpha was present in the cell lysates as 35-kD pro-IL-1 alpha, as determined by Western blot analysis. AM from patients with ILD produced higher levels of LPS-induced cell-associated IL-1 alpha protein (9.78 +/- 1.80 ng/ml, p = 0.031). LPS-induced IL-1 beta production by AM from nonsmoking control subjects (5.22 +/- 1.89 ng/ml) and asymptomatic smokers (4.39 +/- 0.66 ng/ml) was equivalent to total IL-1 alpha protein production.(ABSTRACT TRUNCATED AT 250 WORDS)
Janson
R W
RW
Rheumatology Section, Denver Veterans Administration Medical Center, CO 80220, USA.
Hance
K R
KR
King
T E
TE
D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017563:Lung Diseases, Interstitial / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking / Q000378:metabolism
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor