Influence of Acute Phase Proteins on Neutrophil Function In Vitro

As part of a systemic inflammatory response, acute phase proteins (APPs) are released into the blood to support the body's immune response. Once in the bloodstream, the APPs can also interact with immune cells, such as neutrophil granulocytes (PMNs). However, this interaction is not yet fully understood. This study aims to investigate the effects of specific APPs on various functions of neutrophil granulocytes in vitro. PMNs were isolated from peripheral blood of healthy volunteers and subsequently exposed to varying concentrations of CRP, fibrinogen, or ferritin. As activating agents, TNF-α (TNFα)/N-formylmethionine-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA), or ionomycin were used. Triggered oxidative burst and the expression of surface antigens CD11b, CD62L, and CD66b were measured by flow cytometry. Live cell imaging (LCI) determined the influence of ferritin on migration behavior, time-resolved MPO release, and NET formation. CRP had a certain, non-significant activating effect on PMN oxidative burst and surface epitope expression. Ferritin led to a moderate increase in the oxidative burst, especially after activation with TNF-α/fMLP, PMA, or ionomycin. Ferritin reduced PMN migration without TNFα and enhanced PMN migration in the presence of TNFα. Without TNFα, ferritin prolonged NETosis and had a certain dose-specific effect on MPO release. Fibrinogen mainly influenced the expression of CD11b, CD62L, and CD66b. The observed effects of acute phase proteins on PMNs showed plausible, concentration-dependent, and differential effects for the tested APPs, but only of moderate magnitude. Future experiments should focus on intracellular signaling pathways and on the determination of PMN gene expression profiles. Given the broad context in which APPs are elevated, their interaction with PMNs is of considerable scientific interest for a multitude of clinical conditions.