title: The B-cell superantigen Finegoldia magna protein L causes pulmonary inflammation by a mechanism dependent on MyD88 but not B cells or immunoglobulins.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Pulmonary inflammatory reactions were analyzed at various time points after intratracheal administration of PL to various strains of mice.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Anderson
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Decheng
authors.initials: D
authors.lastname: Song
authors.forename: David
authors.initials: D
authors.lastname: Larosa
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Gerold
authors.initials: G
authors.lastname: Kierstein
authors.forename: Sonja
authors.initials: S
authors.lastname: Kierstein
authors.forename: Angela
authors.initials: A
authors.lastname: Haczku
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Levinson
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology* / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D054360:Chemokine CXCL1 / Q000032:analysis / Q000276:immunology; D054426:Chemokine CXCL2 / Q000032:analysis / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D007136:Immunoglobulins / Q000032:analysis / Q000276:immunology*; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D010462:Peptostreptococcus / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D015850:Interleukin-6; C116593:L-protein, Peptococcus magnus; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D014409:Tumor Necrosis Factor-alpha