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Related Experiment Videos

Elastase from polymorphonuclear leucocytes: a regulatory enzyme in immune complex disease.

G Döring, W Goldstein, K Botzenhart

    Clinical and Experimental Immunology
    |June 1, 1986
    PubMed
    Summary

    Polymorphonuclear leukocyte (PMN) elastase cleaves immune complexes in cystic fibrosis patients, reducing inflammation. This feedback mechanism may explain cyclic inflammatory states in chronic Pseudomonas aeruginosa infections.

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    Area of Science:

    • Immunology
    • Pulmonology
    • Biochemistry

    Background:

    • Cystic fibrosis (CF) patients often experience chronic Pseudomonas aeruginosa lung infections.
    • Chronic inflammation in CF is associated with polymorphonuclear leukocytes (PMN) and immune complexes.
    • The interplay between PMN proteases and immune complexes in CF lung infections is not fully understood.

    Purpose of the Study:

    • To investigate the role of PMN elastase in cleaving immune complexes.
    • To determine if PMN elastase regulates inflammation in CF patients with chronic P. aeruginosa infections.
    • To elucidate the mechanism by which PMN elastase affects immune complexes and inflammatory responses.

    Main Methods:

    • Quantitative determination of lysosomal protease and immune complex activities in sputum from 21 CF patients.

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  • Longitudinal monitoring of reciprocal changes in protease and immune complex levels.
  • In vitro treatment of immune complex-positive sputum with PMN elastase.
  • Analysis of immunoglobulin cleavage, antigen binding, and PMN oxidative burst stimulation.
  • Western blot analysis of immunoglobulin heavy chains.

    • Main Results:

    • A significant inverse correlation was observed between PMN protease activity and immune complex levels.
    • Treatment with PMN elastase reduced IgG and IgA immune complex values.
    • PMN elastase cleaved immunoglobulins in the hinge region, releasing the Fc portion.
    • Cleaved immune complexes did not stimulate the PMN oxidative burst.
    • Cleavage of in vitro immune complexes did not liberate bound antigen.

    Conclusions:

    • PMN elastase cleaves immune complexes in the sputum of CF patients, suggesting a regulatory role in inflammation.
    • This cleavage mechanism, by removing the Fc portion of immunoglobulins, may dampen PMN activation.
    • The findings propose a feedback loop where PMN elastase regulates inflammation, potentially leading to cyclic inflammatory states in chronic P. aeruginosa infections.