Am. J. Respir. Crit. Care Med., Vol 151, No. 5, May 1995, 1613-1620.
Human alveolar macrophages produce predominantly the 35-kD pro-forms of interleukin-1 alpha and interleukin-1 beta when stimulated with lipopolysaccharide
RW Janson, KR Hance and TE King Jr
Rheumatology Section, Denver Veterans Administration Medical Center, CO 80220, USA.
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)
