Serum amyloid A is an activator of PMN antimicrobial functions: induction of degranulation, phagocytosis, and enhancement of anti-Candida activity.
Serum amyloid A (SAA) is a 12-kDa protein secreted in large amounts by liver cells during microbial infections or inflammatory diseases. We have recently reported that SAA induces chemotaxis of polymorphonuclear cells (PMN), monocytes, and T lymphocytes and stimulates their adhesion to endothelial monolayers. In this study, we investigated whether SAA regulates PMN antimicrobial activities. We found that recombinant SAA (rSAA), at concentrations comparable to serum levels attained during an acute phase response, is a potent activator of PMN. Stimulation of PMN by rSAA results in a rapid and transient increase of cytosolic calcium concentration and up-regulation of cell-surface expression of antigens involved in adhesion and microbial recognition such as CD11c and CD16. In addition, stimulation of PMN with rSAA increases secretion of lactoferrin, an antimicrobial protein that is contained in specific granules of PMN and enhances PMN phagocytic activity against heat-killed Candida albicans. Finally, activation of PMN with rSAA enhances their anti-Candida activity within 30 min of stimulation. These results suggest that SAA is involved in up-regulating PMN antimicrobial activities and that high circulating concentrations of SAA as seen in the acute phase response may constitute a potential host defense mechanism against fungal infections.
Badolato
R
R
Clinica Pediatrica, Universitá di Brescia, Italy. badolato@master.cci.unibs.it
Wang
J M
JM
Stornello
S L
SL
Ponzi
A N
AN
Duse
M
M
Musso
T
T
D000210:Acute-Phase Reaction; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001053:Apolipoproteins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015703:Antigens, CD; D001053:Apolipoproteins; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D010566:Virulence Factors, Bordetella; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007781:Lactoferrin; D002118:Calcium