Elicitation of allergic asthma by immunoglobulin free light chains

Aletta D. Kraneveld, Mirjam Kool, Anneke H. Van Houwelingen, Paul Roholl, Alan Solomon, Dirkje S. Postma, Frans P. Nijkamp, Frank A. Redegeld

Research output: Contribution to journalArticle

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Abstract

The observation that only 50% of patients with adult asthma manifest atopy indicates that other inflammatory mechanisms are likely involved in producing the characteristic features of this disorder; namely reversible airway obstruction, hyperresponsiveness, and pulmonary inflammation. Our recent discovery that antigen-specific Ig free light chains (LCs) mediate hypersensitivity-like responses suggests that these molecules may be of import in the pathophysiology of asthma. Using a murine experimental model of nonatopic asthma, we now have shown that an LC antagonist, the 9-mer peptide F991, can abrogate the development of airway obstruction, hyperresponsiveness, and pulmonary inflammation. Further, passive immunization with antigen-specific LCs and subsequent airway challenge can elicit a mast cell-dependent reaction leading to acute bronchoconstriction. These findings, and the demonstration that the concentration of free κ LCs in the sera of patients with adult asthma were significantly increased (as compared with age-matched nonasthmatic individuals), provide previously undescribed insight into the pathogenesis of asthma. In addition, the ability to inhibit pharmacologically LC-induced mast cell activation provides a therapeutic means to prevent or ameliorate the adverse bronchopulmonary manifestations of this incapacitating disorder.

Original languageEnglish (US)
Pages (from-to)1578-1583
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number5
DOIs
StatePublished - Feb 1 2005

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Immunoglobulin Light Chains
Asthma
Light
Airway Obstruction
Mast Cells
Pneumonia
Antigens
Passive Immunization
Bronchoconstriction
Hypersensitivity
Theoretical Models
Peptides
Serum

All Science Journal Classification (ASJC) codes

  • General

Cite this

Elicitation of allergic asthma by immunoglobulin free light chains. / Kraneveld, Aletta D.; Kool, Mirjam; Van Houwelingen, Anneke H.; Roholl, Paul; Solomon, Alan; Postma, Dirkje S.; Nijkamp, Frans P.; Redegeld, Frank A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 5, 01.02.2005, p. 1578-1583.

Research output: Contribution to journalArticle

Kraneveld, AD, Kool, M, Van Houwelingen, AH, Roholl, P, Solomon, A, Postma, DS, Nijkamp, FP & Redegeld, FA 2005, 'Elicitation of allergic asthma by immunoglobulin free light chains', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 5, pp. 1578-1583. https://doi.org/10.1073/pnas.0406808102
Kraneveld, Aletta D. ; Kool, Mirjam ; Van Houwelingen, Anneke H. ; Roholl, Paul ; Solomon, Alan ; Postma, Dirkje S. ; Nijkamp, Frans P. ; Redegeld, Frank A. / Elicitation of allergic asthma by immunoglobulin free light chains. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 5. pp. 1578-1583.
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