Serum metalloproteinase leukolysin (MMP-25/MT-6): a potential metabolic marker for atopy-associated inflammation
ABSTRACT Leukolysin is a novel matrix metalloproteinase (MMP-25/MT-6) released mainly by granulocytic cells, primarily neutrophils, which are implicated in chronic airways inflammation.
To determine if leukolysin might be a serum marker for atopic asthma or chronic obstructive pulmonary disease (COPD).
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.
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.
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.
- SourceAvailable from: Massimo Coletta[Show abstract] [Hide abstract]
ABSTRACT: Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.Molecular Aspects of Medicine 11/2011; 33(2):119-208. DOI:10.1016/j.mam.2011.10.015 · 10.30 Impact Factor
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ABSTRACT: In 2010 over 200 articles were published in Clinical and Experimental Allergy including editorials, reviews, opinion articles, letters, book reviews and of course at the heart of the journal, papers containing original data which have moved the field of allergy forward on a number of fronts. For the third year running the editors felt it would be of value to summarize the key messages contained in these papers as a snapshot of where the cutting edge of research into allergic disease is leading. We have broadly followed the sections of the journal, although this year the mechanistic articles are grouped together and the studies involving experimental models of disease are discussed throughout the paper. In the field of asthma and rhinitis phenotypes and biomarkers continue to a major pre-occupation of our authors. There is continued interest in mechanisms of inflammation and disordered lung function with the mouse model of asthma continuing to offer new insights. There is also a steady flow of papers investigating new therapies, including those derived from plants and herbs, although many are mechanistic with too few high quality clinical trials. The mechanisms involved in allergic disease are well covered with many strong papers using clinical material to ask relevant questions. Pro-pre and snybiotics continue to be of major interest to our authors and this remains a controversial and complicated field. The discipline of epidemiology has retained its interest in risk factors for the development of allergic disease with a view to refining and debating the reasons for the allergy epidemic. There is continued interest in the relationship between helminthic disease and allergy with a new twist in 2010 involving studies using infection with helminths as a potential treatment. The genetics of allergic disease continues to be very productive, although the field has moved on from only investigating single nucleotide polymorphisms of candidate genes to Genome Wide Association Studies and an increasing and welcome emphasis on gene-environment interactions. In the field of clinical allergy there is steady flow of papers describing patterns of drug allergy with renewed interest in reactions to contrast media, but food allergy is the major area of interest in this section of the journal. Lastly in the field of allergens there is a growing interest in the role of component resolved diagnosis in improving the diagnosis and management of allergic disease. Another excellent year, full of fascinating and high quality work, which the journal has been proud to bring to the allergy community.Clinical & Experimental Allergy 12/2011; 41(12):1690-710. DOI:10.1111/j.1365-2222.2011.03892.x · 4.32 Impact Factor
Article: Serum Biomarkers in Elderly Asthma.[Show abstract] [Hide abstract]
ABSTRACT: Abstract Objective: Asthma is usually misdiagnosed and under-treated in the elderly population, resulting in complications and increased severity to the patient. In this review we describe some of the most important serum markers of asthma studied so far, reporting their outcomes and possible prediction of asthma in the elderly population. Methods: The PubMed electronic database was used to search for promising serum biomarkers of asthma studied in original articles published in peer-reviewed journals from 2000 to January 2013. Results: A total of 13 relevant serum biomarkers were selected, including IgE, CRP, high sensitive CRP, IL-6, IL-8, IL-17, TNF-α, neopterin, serum amyloid A, eosinophil cationic protein, leukolysin, YKL-40 and soluble CD86. Conclusions: Although the major focus of treatment and research has been on allergic asthma, several forms of the disease are recognized, such as neutrophilic asthma, which is characteristic of older patients. Different phenotypes imply different treatments and so it becomes important to correctly determine which type of asthma the patient is suffering from. Serum markers capable of supporting a diagnosis of asthma are needed in order to counter mistreatment and misdiagnosis with other obstructive airways disease (OAD) in elderly patients. As convenient as serum markers may seem to be, a marker capable of accurately identifying asthma with sufficient specificity is yet to be found.Journal of Asthma 08/2013; 50(10). DOI:10.3109/02770903.2013.834932 · 1.83 Impact Factor