The relative roles of bacteria and host inflammatory cells in SIgA degradation.
OBJECTIVE
Secretory Immunoglobulin (Ig) A, the most important Ig for lung defense, is highly dependent on its molecular structure for its immune activity. Proteolytic cleavage of SIgA may occur in the airways and render the SIgA molecule inactive. Previous studies have attributed IgA cleavage to neutrophils (polymorphonucleur cells [PMNs]) and other host immunoinflammatory cells in the airways or bacterial pathogens. The resultant IgA degradation leads to airway inflammation and subsequent pneumonia. The aim of this study was to discern the relative roles of host inflammatory cells and bacteria in SIgA cleavage in vitro.


METHODS
SIgA was cocultured with PMNs, PMNs activated with fMLP, monocytes, monocytes pretreated with lipopolysaccharide (LPS), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas, or Acinetobacter alone or with monocyte culture supernatants and PMNs. SIgA cleavage resulted in two fractions, a <75 kDa fraction (secretory component fraction) and an intact SIgA fraction by size exclusion ultrafiltration. This was quantified by ELISA and confirmed by SDS-PAGE.


RESULTS
Neither naïve nor activated PMNs showed any cleavage of SIgA. Unstimulated monocytes or LPS stimulated monocytes also failed to demonstrate fragmentation of SIgA. Only modest SIgA cleavage was noted when both PMNs and monocytes were stimulated before coculture with SIgA but marked SIgA proteolysis was noted with the addition of Pseudomonas or Acinetobacter but not MRSA.


CONCLUSIONS
Bacterial pathogens, but not activated immunoinflammatory cells, were responsible for SIgA degradation in this study. This was evident only with Pseudomonas and Acinetobacter. This may be a virulence factor for pneumonia with these pathogens in vivo.
Diebel
Lawrence N
LN
Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. ldiebel@med.wayne.edu
Liberati
David M
DM
Diglio
Clem A
CA
D040981:Acinetobacter baumannii / Q000276:immunology; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*
D007071:Immunoglobulin A, Secretory