The proinflammatory activity of recombinant serum amyloid A is not shared by the endogenous protein in the circulation.
OBJECTIVE
Elevated serum levels of the acute-phase protein serum amyloid A (SAA) are a marker for active rheumatoid arthritis (RA), and SAA can also be found in the tissues of patients with active RA. Based on a number of studies with recombinant SAA (rSAA), the protein has been suggested to be a potent proinflammatory mediator that activates human neutrophils, but whether endogenous SAA shares these proinflammatory activities has not been directly addressed. The present study was undertaken to investigate whether SAA in the plasma of patients with RA possesses proinflammatory properties and activates neutrophils in a manner similar to that of the recombinant protein.


METHODS
Neutrophil activation was monitored by flow cytometry, based on L-selectin shedding from cell surfaces. Whole blood samples from healthy subjects and from RA patients with highly elevated SAA levels were studied before and after stimulation with rSAA as well as purified endogenous SAA.


RESULTS
Recombinant SAA potently induced cleavage of L-selectin from neutrophils and in whole blood samples. Despite highly elevated SAA levels, L-selectin was not down-regulated on RA patient neutrophils as compared with neutrophils from healthy controls. Spiking SAA-rich whole blood samples from RA patients with rSAA, however, resulted in L-selectin shedding. In addition, SAA purified from human plasma was completely devoid of neutrophil- or macrophage-activating capacity.


CONCLUSIONS
The present findings show that rSAA is proinflammatory but that this activity is not shared by endogenous SAA, either when present in the circulation of RA patients or when purified from plasma during an acute-phase response.
Björkman
Lena
L
Sahlgrenska Academy, University of Gothenburg, Department of Rheumatology and Inflammation Research, Gothenburg, Sweden. lena.i.bjorkman@vgregion.se
Raynes
John G
JG
Shah
Chandrabala
C
Karlsson
Anna
A
Dahlgren
Claes
C
Bylund
Johan
J
D000210:Acute-Phase Reaction / Q000276:immunology* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D018375:Neutrophil Activation / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D019041:L-Selectin