Immunoglobulin a modulates inflammatory responses in an in vitro model of pneumonia.
BACKGROUND
Preservation of mucosal immunity has been shown to affect the risk and outcome of pneumonia in severely injured patients. Secretory immunoglobulin A (SIgA) is the principle humoral defense of mucosal surfaces in the body and has several antiinflammatory properties. Polymorphonuclear neutrophils (PMN) function to kill invading microorganisms, but their exaggerated inflammatory responses may cause tissue injury to the host. The purpose of this study was to compare the ability of different immunoglobulin (Ig) isotypes to modulate PMN cytotoxic potential cocultured with respiratory epithelial cells challenged with bacteria.


METHODS
Calu-3 cell monolayers were established on membranes (0.1-microm pore) in a two-chamber culture system. Escherichia coli (EC) incubated with either polyclonal SIgA or IgG was inoculated into the apical chamber and PMNs (10/mL) added to the basal chamber. PMN cytotoxic potential was indexed by % CD11b expression, superoxide anion (O2) production, and elastase release. Dextran flux was used to index Calu-3 monolayer permeability.


RESULTS
Addition of EC to PMN-Calu-3 cell coculture increased % CD11b expression, O2 production, and elastase release. IgG had no effect on PMN activation after EC challenge. SIgA abrogated PMN activation and the increase in Calu-3 cell monolayer permeability noted with EC or EC + IgG treatment groups.


CONCLUSIONS
PMN cytotoxic potential was decreased by the presence of SIgA but not IgG in an in vitro model to simulate pneumonia in vivo. SIgA may not only function to protect against microbial invasion of mucosal surfaces, but may also protect against tissue injury from an exaggerated inflammatory response.
Diebel
Lawrence N
LN
Department of Surgery, Wayne State University Health Center, Detroit, Michigan 48201, USA. ldiebel@med.wayne.edu
Liberati
David M
DM
Diglio
Clement A
CA
Brown
William J
WJ
D017209:Apoptosis / Q000502:physiology; D039481:CD11b Antigen / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology; D011014:Pneumonia / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D039481:CD11b Antigen; D007071:Immunoglobulin A, Secretory; D014409:Tumor Necrosis Factor-alpha