LEUKOTRIENE A(4) HYDROLASE IN HUMAN BRONCHOALVEOLAR LAVAGE FLUID

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.