Accelerated Fas-mediated apoptosis of monocytes and maturing macrophages from patients with systemic lupus erythematosus: Relevance to in vitro impairment of interaction with iC3b-opsonized apoptotic cells

Impaired handling of apoptotic cells has been suggested as an important fac tor in the development of systemic lupus erythematosus (SLE), and a role fo r complement in the removal of apoptotic cells was shown recently. We studi ed the in vitro function of macrophages from 40 patients with SLE and their matched controls in the removal of heterologous apoptotic cells opsonized by iC3b. Interaction index of apoptotic cells opsonized by iC3b was signifi cantly lower in patients with SLE and averaged 71 % +/- 37 of that of healt hy individuals (p < 0.002) and 69% +/- 35 of patients with rheumatoid arthr itis (p < 0.007). SLE patients had increased apoptosis of both freshly isol ated monocytes (p < 0.001) and maturing macrophages (p < 0.04) that led to decreased density of monocyte- derived macrophages. Apoptosis was inhibited by adding soluble Fas receptor indicating Fas-mediated apoptosis. As demon strated in both healthy controls and patients with SLE, decreased macrophag e density by itself caused significant decreased uptake of apoptotic cells by the remaining macrophages. Maintaining normal density in SLE patients ei ther by an increased initial density or by using soluble Fas restored the i nteraction capacity of the individual macrophages in the majority of patien ts. We concluded that impaired in vitro interaction of iC3b-opsonized apopt otic cells with macrophages from patients with SLE was mainly associated wi th Fas-dependent accelerated apoptosis of the monocytes/macrophages. Accele rated apoptosis of phagocytes may represent a novel in vitro mechanism of i mpairment of interaction with apoptotic cells that, apart from reducing the number of professional phagocytes, alters the function of the remaining ma crophages.