We examined cell-free human bronchoalveolar lavage fluid (BALF) for en
zymes of the 5-lipoxygenase pathway. BALF was obtained from six patien
ts who were active smokers and six nonsmokers. Enzymatic activity in c
ell-free BALF was assessed by specific assays for leukotriene (LT) A(4
) hydrolase, 5-lipoxygenase, and LTC, synthase using HPLC. Only LTA(4)
hydrolase enzymatic activity was found. This activity ranged from 101
to 667 when expressed as picomoles of LTB(4) produced per milliliter
BALF. Enzymatic activity in smokers vs nonsmokers was 484+/-120 vs 129
+/-32 pmol LTB(4)/ml BALF (mean+/-SD, P<0.0001). There were no leukotr
ienes found in BALF before assay. Immunoblot analysis revealed an immu
noreactive band at a relative molecular mass of 69,000 D in all sample
s, consistent with LTA(4) hydrolase, but no evidence of 5-lipoxygenase
. BALF had greater LTA(4) hydrolase activity per milligram of protein
than neutrophil cytosol, epithelial cell cytosol, plasma, or serum. Th
e synthesis of LTB(4) was significantly increased when neutrophils wer
e stimulated in BALF. These data indicate the selective presence of LT
A(4) hydrolase in BALF which is significantly increased in smokers. Th
is enzyme in BALF may contribute to the inflammatory response in tobac
co-related lung disease.