The B-cell superantigen Finegoldia magna protein L causes pulmonary inflammation by a mechanism dependent on MyD88 but not B cells or immunoglobulins
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Objective and design
To determine whether Finegoldia magna protein L (PL) causes lung inflammation and, if so, whether the response is dependent on its immunoglobulin (Ig)-binding B-cell superantigenic property.
Pulmonary inflammatory reactions were analyzed at various time points after intratracheal administration of PL to various strains of mice.
PL caused peribronchial and perivascular inflammation that peaked at 18–24 h. Polymorphonuclear cells (PMNs) began to accumulate in bronchoalveolar lavage fluid (BALF) of PL-challenged mice by 4 h and accounted for >90% of leukocytes by 18–24 h. Inflammation was marked by the appearance of MIP-2, KC, TNF-α, and IL-6 in the BALF with peak levels attained 4 h after PL administration. PL-induced pulmonary inflammation was associated with increased airway hyper-reactivity following inhalation of methacholine. The inflammatory reaction was unabated in mice lacking B cells and immunoglobulins. In contrast, PL-induced inflammation was abrogated in MyD88-deficient mice. PL-induced responses required alveolar macrophages.
These results strongly suggest that PL-induced lung inflammation is dependent on an innate MyD88-dependent pathway rather than the Ig-binding properties of this microbial B cell superantigen. We propose that this pulmonary inflammatory reaction is caused by the interaction of PL with a Toll-like receptor expressed on alveolar macrophages.
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- The B-cell superantigen Finegoldia magna protein L causes pulmonary inflammation by a mechanism dependent on MyD88 but not B cells or immunoglobulins
Volume 61, Issue 2 , pp 161-169
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- SP Birkhäuser Verlag Basel
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- In-vivo inflammation
- Inflammatory mediators
- Innate immunity
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- Author Affiliations
- 1. Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
- 2. Department of Molecular Cell Biology, Vrije Universiteit, VUMC, Amsterdam, The Netherlands