ACTIVATION OF POLYMORPHONUCLEAR NEUTROPHILS BY IMMUNE COMPLEX: POSSIBLE INVOLVEMENT IN THE DEVELOPMENT OF TRANSFUSION-RELATED ACUTE LUNG INJURY

Abstract

Background: Human polymorphonuclear neutrophils (PMNs) are suspected as a causative factor in the development of febrile nonhemolytic transfusion reactions (FNHTRs), such as transfusion-related acute lung injury (TRALI), although the mechanisms underlying FNHTRs have not yet been precisely clarified. The aim of this study was to evaluate the potency of immune complexes (ICs) to activate PMNs and to identify soluble factors produced by PMNs. Methods We: investigated the production of tumor necrosis factor α (TNFα) and perform by PMNs on stimulation with artificial oligomerized ICs by enzymelinked immnosorbent assay (ELISA). Furthermore, the potency of culture supernatants of PMNs that were stimulated with ICs was investigated with regard to the growth inhibitory activity against lung-tissue-derived primary cell culture (LT cells) and cytotoxic activity against LT cells by 3H-thymidine uptake experiment and 4-hour 51Cr release assay, respectively. Findings: PMNs activated by ICs were proved to produce TNFα and perform. The growth of LT cells was inhibited in the presence of cell-free culture supernatants of PMNs cultivated with ICs. Moreover, cell-free culture supernatants of PMNs cultivated with ICs appeared to have cytotoxic activity against LT cells. Conclusion: These results suggest that IC-stimulated PMNs produce inflammatory and cytotoxic mediators, which are potent inducers of FNHTRs such as TRALI.