Cleavage of SIgA by gram negative respiratory pathogens enhance neutrophil inflammatory potential.
OBJECTIVE
Secretory immunoglobulin A (SIgA), the principle immune defense at respiratory and other mucosal sites in the body, is highly dependant on its molecular structure for effective antibody function. Previous studies have demonstrated that gram-negative but not gram-positive isolates from patients with nosocomial pneumonia have IgA protease activity that contributes to the development of infection. We postulate that SIgA cleavage by bacteria would also affect anti-inflammatory properties of IgA and studied this in vitro.


METHODS
Sterile filtrates obtained from Pseudomonas, Acinetobacter, and methicillin resistant Staphylococcus aureus (MRSA) held in culture with SIgA were used to challenge polymorphonuclear neutrophils (PMNs) obtained from healthy volunteers. In a second group of experiments, blood monocytes were incubated with lipopolysaccharide (LPS) or LPS + IgA, and the resulting culture supernatants was used to stimulate PMNs in vitro.


RESULTS
LPS-stimulated monocytes increased CD11b expression, O2-generation and elastase release by PMNs. Secretory IgA but not IgG abrogated this response. Cleavage of SIgA by the gram-negative respiratory isolates, Pseudomonas aeruginosa and Acinetobacter baumanii also led to the loss of cellular effector function noted with intact SIgA. Additionally, PMN cytotoxic potential was similar to that noted with PMNs treated with supernatant from LPS-stimulated monocytes.


CONCLUSIONS
IgA cleavage by gram-negative respiratory isolates may lead to the development of pneumonia and the subsequent severity of the infection as a result of uncontrolled inflammatory responses by the host.
Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. ldiebel@med.wayne.edu
Lawrence N
LN
Diebel
David M
DM
Liberati
Parth B
PB
Amin
Clem A
CA
Diglio
D000704:Analysis of Variance; D015153:Blotting, Western; D039481:CD11b Antigen / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003428:Cross Infection / Q000276:immunology / Q000503:physiopathology; D004591:Electrophoresis, Polyacrylamide Gel; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators; D055624:Methicillin-Resistant Staphylococcus aureus; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D053717:Pneumonia, Ventilator-Associated / Q000276:immunology / Q000382:microbiology; D011336:Probability; D012016:Reference Values
D039481:CD11b Antigen; D007071:Immunoglobulin A, Secretory; D018836:Inflammation Mediators