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Clin Exp Immunol. Apr 1999; 116(1): 174–180.
PMCID: PMC1905219

Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary artery endothelial cells by antibodies against U1-ribonucleoprotein

Abstract

In order to elucidate the pathogenic role(s) of autoantibodies in connective tissue disease (CTD), we examined whether autoantibodies against U1-ribonucleoprotein (RNP) and double-stranded (ds) DNA can up-regulate ICAM-1, ELAM-1 and class I and II MHC molecule expression on pulmonary artery endothelial cells (HPAEC). ICAM-1, ELAM-1 and class II MHC molecule expression on HPAEC cultured in the presence of anti-U1-RNP-containing and anti-dsDNA-containing IgG from CTD patients was up-regulated significantly in comparison with that on HPAEC cultured with IgG from normal healthy volunteers. Affinity chromatographic enrichment and depletion of the anti-U1-RNP antibody content of anti-U1-RNP-containing IgG confirmed that the anti-U1-RNP antibody did up-regulate ICAM-1, ELAM-1 and class II MHC molecule expression. The finding that an IgG F(ab′)2-purified anti-U1-RNP antibody also up-regulated expression of these molecules may indicate that mechanisms other than Fc receptor-mediated stimulation are involved. These in vitro findings suggest that autoantibodies against U1-RNP and dsDNA play important roles in the immunopathological processes leading to the proliferative pulmonary arterial vasculopathy observed in CTD patients with pulmonary hypertension by up-regulating adhesion and class II MHC molecule expression on endothelial cells.

Keywords: anti-U1-ribonucleoprotein antibodies, connective tissue disease, ICAM-1, ELAM-1, MHC molecules

INTRODUCTION

The pathogenic mechanism(s) responsible for vasculopathy in patients with autoimmune connective tissue diseases (CTD) is/are ill-defined. Antibodies against U1-ribonucleoprotein (RNP) and double-stranded (ds) DNA are frequently detected in the sera of CTD patients and have been found to be useful tools for the diagnosis/classification and management of such patients. However, the roles of these autoantibodies in the pathogenesis of CTD are virtually unknown. As well as circulating autoantibodies against U1-RNP, autoantibodies against negatively charged molecules, such as cardiolipin and DNA, have been suggested to be associated with pulmonary hypertension in CTD patients [13]. In a previous study we demonstrated that autoantibodies against U1-RNP and against the negatively charged molecules cardiolipin and dsDNA increased the amounts of cytokines released by or associated with peripheral blood monocytes obtained from patients with CTD, suggesting that these autoantibodies may cause endothelial cell derangement, and lead to proliferative vasculopathy in such patients [4].

Evidence is growing to suggest that cytokine-inducible leucocyte-endothelial adhesion molecules are important in the primary stages of recruitment and migration of leucocytes to sites of inflammation associated with various disease states [5, 6]. Vascular endothelial cells express a number of molecules essential for cell–cell interactions, including ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and ELAM-1 (E-selectin). ICAM-1 is a ligand for the lymphocyte function antigen-1 (LFA-1), which is present on cells of different types, including T and B lymphocytes, macrophages, neutrophils, lymphoid tissue cells and bone marrow elements [7, 8]. Unlike ICAM-1, ELAM-1 is not expressed on multiple leucocyte and non-leucocyte surfaces, but is found on activated vascular endothelial cells [9].

The MHC class I and II molecules are a family of trans-membrane heterodimeric glycoproteins that play central roles in the cellular immune response. In general, class I molecules are present constitutively on virtually all nucleated cells, whereas class II molecules are normally expressed only on dendritic cells, B lymphocytes, macrophages, endothelial cells and a few other types of cell. Moreover, class I and II MHC molecules on endothelial cells are up-regulated by various cytokines [1012], facilitating their participation in the immune reaction.

A number of distinct populations of autoantibodies that induce expression of adhesion molecules on endothelial cells in vitro have been described recently. Polyclonal anti-dsDNA+ IgG from patients with active systemic lupus erythematosus (SLE) enhanced ELAM-1 expression on the plasma membranes of human umbilical vein endothelial cells (HUVEC) [13]. Anti-endothelial cell antibodies from patients with Wegener's granulomatosis (WG) up-regulated ELAM-1, ICAM-1 and VCAM-1 expression and the production of various cytokines after incubation with HUVEC [14]. Moreover, anti-neutrophil cytoplasmic antibody (ANCA)- and anti-nuclear antibody (ANA)-positive sera were demonstrated to up-regulate ICAM-1 on HUVEC and found to be factors involved in the vessel wall inflammation seen in patients with autoimmune vasculitis [15].

The aim of this study was to elucidate whether autoantibodies against U1-RNP and dsDNA can enhance the expression of adhesion and MHC molecules on pulmonary artery endothelial cells (HPAEC) in vitro.

PATIENTS AND METHODS

Patients and sera

Anti-U1-RNP antibody-positive sera that were found to be strongly anti-U1-RNP antibody-positive (range 208–347 arbitrary units (AU)/ml) using a commercially available ELISA kit (MBL, Nagoya, Japan; normal cut-off < 15 AU/ml) from 19 of 350 CTD patients were selected. The age range of these 19 patients was 26–71 years (median 55 years), male/female = 1/18, and seven, two, one, four and five had SLE, systemic sclerosis (SSc), rheumatoid arthritis (RA), mixed connective tissue disease (MCTD) and Sjögren's syndrome (SS), respectively. Thirteen of these 19 sera were also found to be anti-dsDNA antibody-positive using the MBL ELISA kit (range 13–60 U/ml, normal cut-off < 12 U/ml), including one sample, from a patient with MCTD, that had a very high anti-dsDNA antibody titre (> 400 U/ml). Strongly anti-dsDNA antibody-positive sera (range 68– > 400 U/ml) were also selected from 19 other patients (all females) of the same 350 with CTD. The age range of these 19 patients was 24–72 years (median 49 years), and 16, one, one, and one had SLE, SSc, RA and SS, respectively. Five of these 19 sera were also anti-U1-RNP antibody-positive (range 18–161 U/ml). Sera were also obtained from 12 normal healthy volunteers (age 28–51 years, median 39 years, male/female = 2/10). All the serum samples were divided into 2-ml aliquots and stored at −20°C until use.

Purification of IgG from human sera

The IgG fractions were isolated from the anti-U1-RNP antibody- and anti-dsDNA antibody-positive sera of the CTD patients and sera of the normal healthy volunteers using Protein G Sepharose (Pharmacia Fine Chemicals, Hounslow, UK) chromatography. Briefly, 5 ml serum were diluted 1:5 with PBS pH 7.2 (70 mm phosphate and 80 mm NaCl), loaded onto a 2-ml Protein G Sepharose column, which was washed extensively with PBS, the IgG fractions were eluted with 100 mm glycine–HCl buffer pH 3.0 and immediately dialysed extensively against PBS. The dialysed preparations were sterilized by filtration through a nitrocellulose filter (0.22 μm; Millipore Co. Ltd, Bedford, MA).

Anti-U1-RNP antibodies

Extractable nuclear antigen (ENA) was prepared from rabbit thymus acetone powder (Pel-Freez Biologicals, Rogers, AR) by ammonium sulphate fractionation, according to the method reported previously [16], dialysed against PBS containing 1 mm EDTA and 100 μm PMSF and passed through a normal IgG-Sepharose column to remove any substances bound non- specifically to IgG. Then the ENA preparation was applied to a column of CNBr-activated Sepharose (Pharmacia) to which the IgG fraction of serum (from a patient with MCTD) containing a high titre of the anti-U1-RNP antibody only was bound. The bound U1-RNP fraction was eluted from the column with 3 m guanidine–HCl buffer pH 4.8, dialysed extensively with the EDTA–PMSF–PBS solution described above, followed by dialysis against coupling buffer (100 mm NaHCO3 buffer pH 8.3, containing 500 mm NaCl), after which the fraction was coupled with BrCN-activated Sepharose (Pharmacia), according to the manufacturer's instructions.

IgG depleted of anti-U1-RNP (anti-U1-RNP-depleted IgG) was prepared by passing about 50 mg anti-U1-RNP+ IgG preparation in EDTA–PMSF–PBS through a 3-ml U1-RNP-Sepharose column which had been pre-equilibrated with EDTA–PMSF–PBS and collecting the flow-through fraction. Purified anti-U1-RNP antibody preparations (purified anti-U1-RNP) were eluted with 3 m guanidine–HCl buffer pH 4.8. Both anti-U1-RNP-depleted IgG and purified anti-U1-RNP were dialysed against PBS, concentrated to 1 mg/ml by ultrafiltration (Centricon-10; Amicon, Beverly, MA) and sterilized by filtration, as described above. The anti-U1-RNP titres of the anti-U1-RNP-depleted and control IgG preparations were comparable.

F(ab′)2 anti-U1-RNP preparation

IgG F(ab′)2 fragments were prepared by digesting the affinity-purified anti-U1-RNP antibody preparation (IgG/pepsin = 100/3 w/w) with pepsin in 200 mm acetate buffer pH 4.5, at 37°C overnight. The digestion was terminated by adding 100 mm Tris, followed by dialysis against 150 mm Tris–HCl buffer pH 7.6. The digests were eluted from a Protein-G-Sepharose column, the IgG F(ab′)2 fragments that passed through were collected and the purity of the IgG F(ab′)2 fragments was assessed by SDS–PAGE.

Detection of adhesion and MHC molecules on HPAEC by cell ELISA

Cell ELISA for the detection of adhesion and MHC molecules was performed according to the method [15] reported previously with minor modifications. Cultured HPAEC (Clonetics Co. Ltd., CA) between passages 4 and 6 (104 cells/well in EGM-2 medium (Clonetics)) were seeded onto microculture plates (96 wells) and confluent cell monolayers were allowed to form in a 5% CO2 incubator for 48 h at 37°C. The monolayers were incubated with various concentrations (0–1000 pg/ml) of human recombinant IL-1α (rIL-1α; Calbiochem-Novabiochem Corp., CA), IgG fractions (0–200 μg/m1), purified anti-U1-RNP (0–100 μg/ml) or anti-U1-RNP-depleted IgG (0–100 μg/ml) in a 5% CO2 incubator for 20 h at 37°C. The monolayers were fixed with 0.2% v/v glutaraldehyde (200 μl) in PBS for 30 min at room temperature, washed three times with PBS containing 0.05% v/v Tween (PBS–T) and the wells were blocked with Block Ace (40 mg/ml; Dainippon Pharmaceuticals, Osaka, Japan) diluted 1:2 with PBS containing 10% goat serum (200 μl/well) at 37°C for 60 min. Then the wells were washed three times with PBS–T, and 100 μl mouse MoAb against ICAM-1 (250 ng/ml), ELAM-1 (250 ng/ml), class I MHC molecules (500 ng/ml) or class II MHC molecules (500 ng/ml) in PBS containing 10% goat serum were added to each well and incubated at 37°C for 60 min. The wells were washed three times with PBS–T and 100 μl peroxidase-conjugated goat anti-mouse IgG antibody (250 ng/ml) in PBS containing 20% goat serum were added to each well, followed by incubation at 37°C for 60 min. The wells were washed again with PBS–T and 100 μ1 substrate solution (0.4 mg/ml ortho-phenylene-diamine and 0.4 μl/ml 31% H2O2 in 10 mm citrate/20 mm phosphate buffer pH 4.0) were added, followed by incubation for 5–20 min at room temperature. The colour reaction was stopped by adding 100 μl of 2.5 mH 2SO4 and the absorbance at 490 nm of the solution in each well was read using an automatic ELISA reader (ImmunoMini NJ-2300; Nalge Nunc Int. Co. Ltd., Japan).

Statistical analysis

The data are expressed as means ± s.d. Differences between medians were analysed statistically using the Mann–Whitney U-test and Spearman's rank correlation test and those at P < 0.05 were considered significant.

RESULTS

Effects of rIL-1α on adhesion and MHC molecule expression on HPAEC

ICAM-1, ELAM-1 and class I MHC molecule expression on HPAEC, measured by ELISA, increased in a concentration- dependent manner in response to incubation with rIL-1α at concentrations of 0–10 ng/ml, for 20 h(Fig. 1). Class II MHC molecule expression was not induced by rIL-1α.

Fig 1
Expression of adhesion (ICAM-1 and ELAM-1) and MHC (class I and II) molecules on pulmonary artery endothelial cells (HPAEC) incubated with various concentrations of rIL-1α. Bars show the mean ± s.d. of quadruplicate experiments.

Effects of IgG fractions on adhesion and MHC molecule expression on HPAEC

As shown in Fig. 2, ICAM-1 and ELAM-1 expression on HPAEC, measured by ELISA, increased concentration-dependently in response to incubation with 0, 20 and 200 μg/ml anti-U1-RNP+ IgG (n = 19), anti-dsDNA+ IgG (n = 19) and control IgG from normal healthy volunteers (n = 12). In comparison with the expression levels of HPAEC incubated with 200 μg/ml control IgG, the anti-U1-RNP+ and anti-dsDNA+ IgGs (both 200 μg/ml) significantly up-regulated the expression of ICAM-1 ((Fig. 2a) P < 0.01 and P < 0.05, respectively) and ELAM-1 ((Fig. 2b) P < 0.001 and P < 0.05, respectively).

Fig 2
(See next page) Expression of adhesion and MHC molecules on pulmonary artery endothelial cells (HPAEC) incubated with various concentrations of anti-U1-RNP+ (n = 19), anti-dsDNA+ (n = 19) and control (n = 10) IgGs. The addition of 200 μg/ml anti-U1-RNP ...
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Class II MHC molecule expression on HPAEC increased concentration-dependently in response to incubation with anti-U1-RNP+, anti-dsDNA+ and control IgGs, at concentrations of 0, 20 and 200 μg/ml. In comparison with the corresponding control levels, the anti-U1-RNP+ IgG (200 μg/ml) significantly up- regulated class II MHC molecule expression on HPAEC ((Fig. 2d) P < 0.01), whereas class I MHC molecule expression (Fig. 2c) on HPAEC was not increased significantly by any of the IgG preparations at the concentrations examined.

Effects of purified anti-U1-RNP on adhesion and MHC molecule expression on HPAEC

As shown in Fig. 3, the purified anti-U1-RNP preparations up-regulated the expression of ICAM-1(Fig. 3a), ELAM-1 (Fig. 3b) and class II MHC (Fig. 3d), but not that of class I MHC (Fig. 3c), molecules on HPAEC in a concentration-dependent manner, whereas the anti-U1-RNP-depleted IgG preparations did not up-regulate the expression of any of these molecules.

Fig 3
Expression of adhesion and MHC molecules on pulmonary artery endothelial cells (HPAEC) incubated with various concentrations of purified anti-U1-RNP and anti-U1-RNP-depleted IgG. Purified anti-U1-RNP, but not anti-U1-RNP-deleted IgG, up-regulated ICAM-1 ...

Analysis of the relationships between adhesion and MHC molecule expression in response to the addition of purified anti-U1-RNP (100 μg/ml) revealed a significant correlation between ICAM-1 and ELAM-1 expression (n = 13, rs = 0.859, P < 0.01). However, although the expression of ICAM-1 and class II mhC molecules (rs = 0.402) and ELAM-1 and class II MHC molecules (rs = 0.451) showed a tendency towards a positive correlation, neither correlation reached significance.

Effects of IgG F(ab′)2-purified anti-U1-RNP on ICAM-1 expression on HPAEC

As shown in Table 1, IgG F(ab′)2-purified anti-U1-RNP up-regulated ICAM-1 expression concentration-dependently and almost as effectively as intact purified anti-U1-RNP at the same molar concentrations, whereas anti-U1-RNP-depleted IgG did not up-regulate ICAM-1 expression.

Table 1
Effect of intact and F(ab′)2 IgG anti-U1-RNP and anti-U1-RNP-depleted IgG on ICAM-1 expression after incubation with pulmonary artery endothelial cells (HPAEC) (mean optical density of duplicate experiments read at 490 nm is represented)

DISCUSSION

The results of this study demonstrated that anti-U1-RNP+ and anti-dsDNA+ IgGs from patients with CTD up-regulated the expression of ICAM-1, ELAM-1 and class II MHC molecules on the surfaces of HPAEC. Moreover, intact and F(ab′)2 IgG anti-U1-RNP purified by affinity chromatography also enhanced the expression of these molecules. Up-regulation of ICAM-1 and ELAM-1 expression on HPAEC by anti-U1-RNP antibodies suggests their pathogenic role in vasculopathy by affecting the migration and adhesion of neutrophils to the vascular endothelium. Up-regulation of class II MHC expression on HPAEC by anti-UI-RNP antibodies suggests their pathogenic role invasculopathy by recruitment of CD4+ T cells.

Recently, a number of distinct populations of autoantibodies that induced the expression of adhesion molecules on endothelial cells in vitro have been described. The reported effects of polyclonal anti-dsDNA+ IgG from patients with SLE on the expression of adhesion molecules on HUVEC are inconsistent. One study showed that expression of ELAM-1 on HUVEC was enhanced and that of VCAM-1 was reduced by polyclonal anti-dsDNA+ IgG [13], whereas another demonstrated that such IgG enhanced the expression of ICAM-1 and VCAM-1, but reduced that of ELAM-1, on HUVEC by polyclonal anti-dsDNA+ IgG [17]. In contrast, we found that anti-dsDNA+ IgG up-regulated both ICAM-1 and ELAM-1 expression on HPAEC and these differing results may be due to the different organs (i.e. pulmonary artery versus umbilical vein) from which the endothelial cells originated. Anti-endothelial cell antibodies derived from patients with WG were found to up-regulate the expression of ELAM-1, ICAM-1 and VCAM-1 and the production of various cytokines after incubation with HUVEC [14]. Moreover, ANCA+ and ANA+ sera were shown to up-regulate ICAM-1 expression on HUVEC and found to be factors involved in vessel wall inflammation seen in patients with autoimmune vasculitis [15].

Possible mechanisms by which anti-U1-RNP autoantibodies enhance the expression of adhesion and MHC molecules are: (i) anti-U1-RNP antibodies may penetrate the endothelial cells and react with their subcellular target antigen, and (ii) these antibodies may bind to their target epitope or cross-reactive molecules present on the surfaces of endothelial cells. With regard to the former hypothesis, anti-U1-RNP IgG was demonstrated to penetrate viable human mononuclear cells via their surface Fc receptors and to react with their nuclear RNP [18]. Ma et al. [19] reported that significantly more anti-U1-RNP IgG than anti-SS-A IgG, anti-SS-B IgG or pooled control IgG entered lymphocytes and showed that the entry of anti-RNP IgG into T cells was mediated by the F(ab′)2, rather than the Fc portion of the IgG molecule. They showed that whole U1-RNP polypeptide and its heterodimer receptor were present on the surface of T cells [20]. It has been suggested that endogenous autoantigens are probably present on MHC class II molecules and are recognized by the corresponding T cells, which are tolerant under normal circumstances [21]. One hypothesis, that anti-U1-RNP antibodies bind to processed fragments of U1-RNP presented by MHC class II molecules and this leads to the activation of a secondary signal transduction mechanism, remains to be verified. In contrast to our previous findings with peripheral blood monocytes [4], in this study cytokine production by HPAEC did not increase significantly in response to stimulation with purified anti-U1-RNP alone (data not shown). However, it is possible that very small quantities of cytokines are sufficient to up-regulate adhesion and MHC molecule expression.

Our ELISA methods were confirmed to measure cell surface molecules accurately by including a number of controls, i.e. omitting the mouse MoAb, irrelevant mouse MoAb and polyclonal mouse IgG (data not shown). The finding that the expression of class I MHC molecules was not enhanced by IgG fractions or purified IgG anti-U1-RNP antibody also seems to rule out the potential augmentation of background binding by IgG fractions.

Sterilization of the antibody samples by filtration through a nitrocellulose filter would have effectively prevented any potential contamination by non-specifically aggregated IgG or immune complexes. Furthermore, any endotoxin that might have contaminated the autoantibody preparations was confirmed to be effectively removed by Protein G-Sepharose column chromatography.

It is still unclear whether there are anti-RNP (anti-DNA) antibodies which cause pulmonary hypertension and others which are non-pathogenic. We have found that expression of adhesion molecules and class II MHC molecules is enhanced by anti-U1-RNP IgG fractions which are obtained from patients with pulmonary hypertension, especially those that have concomitant anti-dsDNA antibody activity.

In conclusion, the up-regulation of adhesion and MHC molecule expression on endothelial cells in vitro induced by autoantibodies against U1-RNP and those against negatively charged molecules may initiate the immunopathological processes and lead to the proliferative vasculopathy associated with the pulmonary hypertension in patients with CTD.

Acknowledgments

The authors are grateful to Ms Michiyo Shimizu for technical assistance, and Ms Midori Horibe and Ms Hiromi Hata for secretarial help.

References

1. Asherson RA. Pulmonary hypertension in systemic lupus erythematosus. J Rheumatol. 1990;17:414–5. [PubMed]
2. Luchi ME, Asherson RA, Lahita RG. Primary idiopathic pulmonary hypertension complicated by pulmonary arterial thrombosis. Association with antiphospholipid antibodies. Arthritis Rheum. 1992;35:700–5. [PubMed]
3. Asherson RA, Higenbottam TW, Xuan ATD, Khamashta MA, Hughes GRV. Pulmonary hypertension in a lupus clinic: experience with twenty-four patients. J Rheumatol. 1990;17:1292–8. [PubMed]
4. Okawa-Takatsuji M, Aotsuka S, Uwatoko S, Sumiya M, Yokohari R. Enhanced synthesis of cytokines by peripheral blood monocytes cultured in the presence of autoantibodies against U1-ribonucleoprotein and/or negatively charged molecules: implication in the pathogenesis of pulmonary hypertension in mixed connective tissue disease (MCTD) Clin Exp Immunol. 1994;98:427–33. [PMC free article] [PubMed]
5. Montefort S, Holgate ST. Adhesion molecules and their role in inflammation. Respir Med. 1991;85:91–99. [PubMed]
6. Wegner CD, Gundel RH, Reilly P, Haynes N, Gordon LL, Rothlein R. ICAM-1 in the pathogenesis of asthma. Sci. 1990;247:456–9. [PubMed]
7. Kurzinger K, Reynolds T, Germains R, Ddarignan D, Martz E, Springer TA. A novel lymphocyte function-associated antigen [LFA-1]: cellular distribution, quantitative expression and structure. J Immunol. 1981;27:596–602. [PubMed]
8. Rothlein R, Czajkowski M, O'Neill M, Marlin SD, Mainolfi E, Merluzzi VJ. Induction of ICAM-1 on primary and continuous cell lines by proinflammatory cytokines. J Immunol. 1988;141:1665–9. [PubMed]
9. Bevilacqua MP, Stengelin S, Gimbrone MA, Seed B. ELAM-1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Sci. 1989;243:1160–4. [PubMed]
10. Collins T, Lapierre LA, Fiers W, Strominger JL, Pober JS. Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A, B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci USA. 1986;83:446–50. [PMC free article] [PubMed]
11. Pober JS, Gimbrone MA, Jr, Lapierre LA, Mendrick DL, Fiers W, Rothlein R, Springer TA. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor and immune interferon. J Immunol. 1986;137:1893–6. [PubMed]
12. Pober JS, Lapierre LA, Stolpen AH, et al. Activation of cultured human endothelial cells by recombinant lymphotoxin: comparison with tumor necrosis factor and interleukin 1 species. J Immunol. 1987;138:3319–24. [PubMed]
13. Chan TM, Yu PM, Tsang KLC, Cheng IKP. Endothelial cell binding by human polyclonal anti-DNA antibodies: relationship to disease activity and endothelial alterations. Clin Exp Immunol. 1995;100:506–13. [PMC free article] [PubMed]
14. Papa ND, Guidali L, Sironi M, et al. Anti-endothelial cell IgG antibodies from patients with Wegener's granulomatosis bind to human endothelial cells in vitro and induce adhesion molecule expression and cytokine secretion. Arthritis Rheum. 1996;39:758–66. [PubMed]
15. Johnson PA, Alexander HD, McMillan SA, Maxwell AP. Up-regulation of the endothelial cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1) by autoantibodies in autoimmune vasculitis. Clin Exp Immuno1. 1997;108:234–42. [PMC free article] [PubMed]
16. White PJ, Gardner WD, Hoch SO. Identification of the immunogenically active components of the Sm and RNP antigens. Proc Nat1 Acad Sci USA. 1981;78:626–30. [PMC free article] [PubMed]
17. Lai KN, Leung JCK, Lai KB, Wong KC, Lai CKW. Upregulation of adhesion molecule expression on endothelial cells by anti-DNA autoantibodies in systemic lupus erythematosus. Clin Immunol Immunopathol. 1996;81:229–38. [PubMed]
18. Alarcon-Segovia D, Ruiz-Arguelles A, Fishbein E. Antibody to nuclear ribonucleoprotein penetrates live human mononuclear cells through Fc receptors. Nature. 1978;271:67–69. [PubMed]
19. Ma J, Chapman GV, Chen SL, Melick G, Penny R, Breit SN. Antibody penetration of viable human cells. 1. Increased penetration of human lymphocytes by anti-RNP IgG. Clin Exp Immunol. 1991;84:83–91. [PMC free article] [PubMed]
20. Ma J, King N, Chen SL, Penny R, Breit SN. Antibody penetration of viable human cells. II. Anti-RNP antibodies binding to RNP antigen expressed on cell surface, which may mediate the antibody internalization. Clin Exp Immunol. 1993;93:396–404. [PMC free article] [PubMed]
21. Calin-Laurens V, Forquet F, Lombard-Platet S, Beertolino P, Isabelle C, Trescol-Biemont MC, Gerlier D, Rabourdin-Combe C. High efficiency of endogenous antigen presentation by MHC class II molecules. Int Immunol. 1992;4:1113–21. [PubMed]

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