Detection of a novel macrophage-derived mucus secretagogue (MMS-68) in bronchoalveolar lavage fluid of patients with asthma.

Abstract

We have previously described a novel high-molecular-weight macrophage-derived mucus secretagogue (MMS-68) that causes mucuslike glycoconjugate release from cultured airways, nasal explants, and the Ishikawa adenocarcinoma cell line. We have generated monoclonal antibodies against MMS-68 and have developed an antigen-capture ELISA to measure MMS-68 levels in biologic fluids. Using this ELISA, we have demonstrated elevated levels of MMS-68 in the bronchoalveolar lavage fluid (BALF) of smokers and persons chronic bronchitis, in a patient with asthma and bronchorrhea, and in nasal lavage from patients with allergic rhinitis challenged with histamine and methacholine. We have also demonstrated 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 normal control subjects. To delineate further a role for MMS-68 in the regulation of mucus secretion in asthma, we measured MMS-68 levels in the BALF of 37 patients with non-steroid-dependent asthma and of 16 control subjects. There were 21 men and 16 women in the asthma group (age range, 17 to 62 years; mean, 33.8 years) and 11 men and five women in the control group (age range, 18 to 42 years; mean, 27.8 years). There were no statistical differences in either total cell count (145.5 x 103 +/- 75.7 cells/mm3 x 10(3) cells/mm3 vs 134 x 103 +/- 65.9 x 10(3) cells/mm3, p < 0.234) or numbers of alveolar macrophages (103.7 x 10(3) +/- 71.7 x 10(3)/mm3 vs 98.7 x 10(3) +/- 65 x 10(3) cells/mm3, 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 micrograms MMS-68 per milligram protein compared with 2.09 +/- 0.26 micrograms MMS-68 per milligram protein (p < 0.256) in the control group. There was no correlation between MMS-68 levels and total protein content, numbers of alveolar macrophages, or the production of other macrophage-derived cytokines including interleukin-1, interleukin-6, or tumor necrosis factor in the asthmatic BALF. Mild asthma, which is clinically not associated with mucus hypersecretion, was not associated with elevated levels of MMS-68. We believe that direct correlation exists between mucus hypersecretion and MMS-68 levels.