Interactions of C-Reactive Protein and Serum Amyloid P Component with Interleukin-8 and Their Role in Regulation of Neutrophil Functions.
C-reactive protein (CRP) and serum amyloid P component (SAP) are acute phase proteins, whose concentrations increase within 24 h of inflammation along with concentration of IL-8. Polymorphonuclear neutrophil leukocytes (PMNs) form the earliest barrier protecting an injured organ during acute phase response. The aim of present work was to study interactions between CRP, SAP and IL-8, and to estimate the role of these interactions in regulation of neutrophil transendothelial migration. The results have shown that IL-8 binds to immobilized but not to free CRP. Binding of IL-8 to immobilized SAP was less strong. SAP like IL-8 increased CD11/CD18 integrin expression. IL-8 did not abolish the effect of SAP, and the mixture of IL-8 and SAP has stimulated CD11/CD18 expression. CRP upregulated CD18 but not CD11b expression. Under simultaneous action of CRP and IL-8, the stimulatory effect on CD11b and CD18 was abolished. The expression of fibronectin receptor was reduced by either IL-8 or CRP but increased by SAP. Effect of each protein was downregulated after following preincubations: CRP+SAP, CRP+IL-8 or SAP+IL-8. The mixtures of CRP with SAP, CRP with IL-8 or SAP with IL-8 showed no chemotactic activity, although each of the proteins was chemoattractive. Thus, acute phase proteins and IL-8 can act as anti-inflammatory factors upon binding each other. In summary, CRP and SAP influence PMN adhesion, migration and expression of CD11b/CD18 and fibronectin receptors, and can modulate the action of IL-8 on PMN attachment to endothelium and fibronectin, and on PMN traffic through the extracellular matrix during transendothelial migration.
Galkina
Elena V.
EV
Institute of Experimental Medicine, Russian Academy of Medical Sciences, Saint Petersburg, Russia.
Nazarov
Peter G.
PG
Polevschikov
Alexander V.
AV
Berestovaya
Larissa K.
LK
Galkin
Vitold E.
VE
Bychkova
Natalia V.
NV