Serum metalloproteinase leukolysin (MMP-25/MT-6): a potential metabolic marker for atopy-associated inflammation.

BACKGROUND

Leukolysin is a novel matrix metalloproteinase (MMP-25/MT-6) released mainly by granulocytic cells, primarily neutrophils, which are implicated in chronic airways inflammation.

OBJECTIVE

To determine if leukolysin might be a serum marker for atopic asthma or chronic obstructive pulmonary disease (COPD).

METHODS

Three study populations were evaluated: (1) nuclear families with medical history of atopic asthma (N=337), (2) married-in individuals from an independent study of asthma genetics (N=122) and (3) randomly selected males with diagnosis of COPD (N=100). Each person was screened for asthma or COPD symptoms, respiratory function by standardized spirometry and serum total IgE and leukolysin and anti-IL1 levels by immunoassay. Study groups (1 and 2) were also screened by skin prick test using a battery of 14 common aeroallergens. Heritability estimates for leukolysin and total IgE were made by variance components analysis.

RESULTS

For those without asthma or who had asthma defined as having symptoms, a physician's diagnosis and bronchial hyper-reactivity as demonstrated by reversibility in response to albuteral and/or bronchial reactivity as measured by a methacholine challenge, serum leukolysin levels were found to be higher for those with any positive skin test result. This paralleled trends for serum total IgE. In the nuclear families and COPD patients, serum leukolysin levels were significantly elevated for those who also had elevated total IgE levels (log[IgE]>2.0) compared with those with lower IgE (log[IgE]<2.0). Serum IL-1 levels correlated with the leukolycin levels. In contrast to IgE, leukolysin showed no apparent inherited component.

CONCLUSION

Among individuals with history of chronic airways inflammation (asthma and COPD) serum leukolysin may be a metabolic marker associated with chronic atopy-associated respiratory inflammation. Common factors may stimulate increased production or release of both leukolysin from myeloid cells and IgE from lymphoid cells.