DETECTION OF A NOVEL MACROPHAGE-DERIVED MUCUS SECRETAGOGUE (MMS-68) IN BRONCHOALVEOLAR LAVAGE FLUID OF PATIENTS WITH ASTHMA

Background: We have previously described a novel high-molecular-weight macrophage-derived mucus secretagogue (MMS-68) that causes mucuslike glycoconjugate release front cultured airways, nasal explants, and the Ishikawa adenocarcinoma cell line. We have generated monoclonal antib odies against MMS-68 and have developed an antigen-capture ELISA to me asure MMS-68 levels in biologic fluids. Using this ELISA, we have demo nstrated elevated levels of MMS-68 in the bronchoalveolar lavage fluid (BALF) of smokers and persons chronic bronchitis, in a patient with a sthma and bronchorrhea, and in nasal lavage from patients with allergi c rhinitis challenged with histamine and methacholine. We have also de monstrated that both spontaneous and lipopolysaccharide induced MMS-68 production is increased in the culture supernatants of monocytes from patients with steroid-dependent asthmas compared with those from norm al control subjects. Methods: To delineate further a role for MMS-68 i n the regulation of mucus secretion in asthma, we measured MMS-68 leve ls in the BALF of 37 patients with non-steroid-dependent asthma and of 16 control subjects. Results: There were 22 men and 16 women in the a sthma group (age range, 17 to 62 years; mean, 33.8 years) and 11 men a nd five women in the control group (age range, 18 to 42 years; mean, 2 7.8 years). There were no statistical differences in either total cell count (145.5 x 103 +/- 75.7 cells/mm(3) x 10(3) cells/mm(3) vs 134 x 10(3) +/- 65.9 x 10(3) cells/mm(3), p < 0.234) or numbers of alveolar macrophages (103.7 x 10(3) +/- 71.7 x 10(3)/mm(3) vs 98. 7 x 10(3) +/- 65 x 10 cells/mm(3), p < 0.244) when the asthmatic group was compared with the control group. The MMS-68 level in the asthmatic group was 2 .1 +/- 0.25 mu g MMS-68 per milligram protein compared with 2.09 +/- 0 .26 mu g MMS-68 per milligram protein (p < 0.256) in the control group . Conclusions: There was no correlation between MMS-68 levels and tota l protein content, numbers of alveolar macrophages, or the production of other macrophage-derived cytokines including interleukin-1, interle ukin-5 or tumor necrosis factor in the asthmatic BALF. Mild asthma, wh ich is clinically not associated with mucus hypersecretion, was not as sociated with elevated levels of MMS-68. We believe that direct correl ation exists between mucus hypersecretion and MMS-68 levels.