Biomedical subjects

E Reefman

Publications and source records attributed to E Reefman.

3 recordsLinked to original sources

PubMed2005

Skin sensitivity to UVB irradiation in systemic lupus erythematosus is not related to the level of apoptosis induction in keratinocytes.

OBJECTIVES: Accumulation of apoptotic cells has been suggested to be involved in the pathogenesis of systemic lupus erythematosus (SLE). As sunlight exposure is one of the factors that can trigger disease activity, we hypothesized that UV light may induce increased numbers of apoptotic cells in SLE. METHODS: Fourteen SLE patients and 16 controls were irradiated with UVB to determine their minimal erythemal dose (MED). Subsequently, skin was irradiated with 1 MED and 2 MED, respectively, and after 24 h skin biopsies were analysed immunohistologically for the number of apoptotic cells and presence of pyknotic nuclear debris. RESULTS: MED was significantly decreased in SLE patients and the presence of decreased MED was associated with a history of butterfly rash. Decreased MED was not related to other skin-related ACR criteria or to autoantibody specificities. No differences were detected in the numbers of apoptotic keratinocytes between patients and controls or in the amount of pyknotic nuclear debris following 1 and 2 MED irradiation, respectively. Absolute UVB doses were correlated with the number of apoptotic keratinocytes; dose-responses did not differ significantly between patients and controls. CONCLUSIONS: Increased sensitivity of SLE patients to UVB, although associated with a history of malar rash, is not related to increased induction of apoptosis or increased levels of secondary necrosis in the skin. Thus, compared with controls, UVB-induced apoptosis is not increased in SLE patients under physiological conditions.

Adult↗

PubMed2005

Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement.

BACKGROUND: Defects in phagocytosis of apoptotic cells have a role in the pathogenesis of autoimmune diseases. Decrease of phagocytosis of apoptotic cells occurs in systemic lupus erythematosus (SLE). Factors underlying this decrease are, presently, unknown. OBJECTIVE: To analyse the expression of relevant membrane receptors of monocyte derived macrophages (MDM) from patients with SLE and assess their ability to phagocytose apoptotic cells in comparison with MDM from healthy controls. Additionally, to compare phagocytosis in the presence of SLE sera with that in normal human serum (NHS). METHODS: Human peripheral blood monocytes were isolated from patients and controls, and cultured for 7 days to obtain MDM. Membrane expression of CD14, CD18, CD36, and CD51/61 was measured. MDM were incubated with apoptotic Jurkat cells in the presence of NHS or serum from patients with active or inactive disease. RESULTS: No differences in phagocytosis capacity were found between MDM from patients and controls. Membrane expression of the respective receptors was comparable in patients and controls. However, when MDM from controls were incubated with apoptotic cells in patient serum, phagocytosis was significantly decreased in comparison with incubation in NHS. This effect depended on the patients' disease activity and could be reversed by addition of NHS. Reduced uptake of apoptotic cells was associated with decreased levels of complement C1q, C4, and C3, but not with levels of complement factor B. CONCLUSIONS: Reduced uptake of apoptotic cells by MDM from patients with SLE is not an intrinsic defect but is serum dependent and associated with decreased levels of C1q, C4, and C3.

Adult↗

PubMed1999

The alternatively spliced CD64 transcript FcgammaRIb2 does not specify a surface-expressed isoform.

Three highly homologous genes (A, B and C) and six transcripts have been identified for the class I human IgG receptor (CD64). The hFcgammaRIa1 isoform encodes the prototypic high-affinity receptor for IgG. The alternatively spliced hFcgammaRIb2 transcript was postulated to exist as a second surface-expressed CD64 isoform on myeloid cells. In this report we assessed this proposed role for hFcgammaRIb2 in detail. As CD64 monoclonal antibodies might not recognize hFcgammaRIb2, we tagged the receptor with an hemagglutinin tag and transfected hFcgammaRIb2tag in the presence of FcR gamma-chain into IIA1.6 cells. Both transcript and protein of hFcgammaRIb2tag were clearly present in transfectants. However, in contrast to the (control) hFcgammaRIa1tag, no surface expression of hFcgammaRIb2tag was detectable with a tag-specific monoclonal antibody. Confocal scan laser microscopy revealed hFcgammaRIb2tag to be retained in the endoplasmic reticulum, resulting in absent plasma membrane expression. These results show hFcgammaRIb2 neither to be surface expressed, nor to represent a separate CD64 isoform. This finding, furthermore, implicates that other FcR transcripts defined at the mRNA level may not represent true FcR isoforms either.

Alternative Splicing↗