| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Departments of Obstetrics/Gynecology (S.W.K., N.H.) and Microbiology/Immunology (S.W.K., T.F.H., A.N.), Virginia Commonwealth University/Medical College of Virginia, Richmond, Virginia 23298
Address all correspondence and requests for reprints to: Dr. Scott Kauma, Departments of Obstetrics/Gynecology and Microbiology/Immunology, Virginia Commonwealth University/Medical College of Virginia, Box 980034, Richmond, Virginia 23298.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Fas ligand (FasL) and its receptor, Fas, are known to play an important role in regulation of the immune response. Fas is a type I membrane protein that belongs to the tumor necrosis factor and nerve growth factor receptor family (5). Fas is highly expressed on activated T cells and B cells, NK cells, and macrophages. FasL is a type II membrane protein also related to the tumor necrosis factor family (5). FasL can either be membrane bound (42–48 kDa form) or can be cleaved by metalloproteinases to release the extracellular portion as soluble FasL (sFasL), which is 26 kDa in size (6). FasL is expressed by activated T cells, cytotoxic T lymphocytes, sertoli cells of the testis, and corneal epithelium and endothelium (7, 8, 9). The major function of Fas/FasL interaction and Fas activation is the induction of cell apoptosis (10).
Recent studies have demonstrated that the immunoprivileged nature of the testis and anterior chamber of the eye is caused by the expression of FasL in these tissues. When T cells are activated by infection or foreign antigens, they express Fas. Activation of T cells in the testis or anterior chamber of the eye results in apoptosis of these cells secondary to the local production of FasL (8, 9). The immunoprotective effect of FasL has recently been exploited in transplantation biology by transfecting myoblasts with FasL complementary DNA (11). Cotransplantation of these FasL-expressing myoblasts with pancreatic islet cells into donor mice of a different strain resulted in functional islet cells that were not rejected by the host immune system. These studies demonstrate the importance of Fas/FasL in peripheral localized immunotolerance to foreign antigens. These findings also suggest that Fas/FasL could be a very elegant mechanism for local maternal immunotolerance of the fetal semiallograft during pregnancy.
To test the hypothesis that Fas/FasL interaction is a mechanism in human maternal immunotolerance to the fetus, we first characterized the expression of Fas/FasL in tissues at the maternal-fetal interface. Subsequently, we used human ED27 trophoblast cells and lymphocytes from newborn cord blood as a model to determine whether FasL-expressing trophoblast cells could induce apoptosis in activated lymphocytes in vitro.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The protocol for this study was approved by our institution’s
Committee for the Conduct of Human Research before obtaining any tissue
samples. Term placentas (37–40 weeks gestation) were obtained from
patients undergoing uncomplicated repeat cesarean section. Early
second-trimester placentas (14–20 weeks gestation) were obtained from
patients undergoing elective surgical pregnancy terminations. A
first-trimester human trophoblast cell line (ED27 cells, a
generous gift from Dr. Douglas Kniss, Dept. of Obstetrics and
Gynecology, Ohio State University College of Medicine) was
maintained in DMEM/F12 (Gibco BRL, Grand Island, NY) with
15% FBS. A fetal skin fibroblast cell line (WS1 cells,
ATCC, Rockville, MD) were maintained in MEM
(Gibco BRL) with 10% FBS.
Immunolocalization of Fas, FasL, and CD45
Immunohistochemical staining for Fas was performed on 10-µm frozen sections of placenta (N = 5) post-fixed in acetone at 4 C for 10 min. The primary antibody that was used for Fas detection was a mouse monoclonal antihuman Fas antibody (2 µg/mL, PharMingen, Los Angeles, CA). Immunohistochemical staining for FasL was performed on formalin-fixed, paraffin-embedded 5-µm sections of placenta using a rabbit IgG anti-FasL antibody (0.5 µg/mL; Santa Cruz Biotechnology, Inc., Santa Cruz, CA). Localization of the primary antibody was performed using the Elite kit (Vector Laboratories, Inc., Burlingame, CA) and diaminobenzidine as the color substrate. The sections were then counterstained with hematoxylin. Negative controls included preabsorption of the primary antibody with excess FasL peptide (Santa Cruz Biotechnology, Inc.) or substituting the specific primary antibody with nonspecific antibody of the same isotype and concentration.
Colocalization of Fas and CD45 (leukocyte common antigen) was performed using a modification of the EnVison Doublestain System (DAKO Corp., Carpinteria, CA) on 10-µm frozen tissue sections. After blocking the slide for endogenous peroxidase activity and nonspecific binding, 1 µg/mL anti-Fas antibody (PharMingen) was incubated with the tissue sections for 1 h and detected using the HRP-labeled antibody polymer and diaminobenzidine as substrate. The tissue sections were then again blocked for nonspecific binding and for endogenous biotin (Vector Laboratories, Inc.), followed by incubation with anti-CD45 antibody (400 ng/mL, Novocastra Laboratories, Newcastle, UK) for 1 h. The CD45 antibody was detected by incubating the slides with biotinylated antimouse antibody (1:200, Vector Laboratories, Inc.), followed by strepavidin-Texas Red (10 µg/mL, Molecular Probes, Inc., Eugene, OR). Colocalization of Fas and CD45 was accomplished by photographing the tissue section using fluorescence microscopy (CD45), immediately followed by bright-field photomicroscopy (Fas) of the same microscopic field. Specificity controls consisted of substituting the anti-Fas and/or the anti-CD45 antibodies with nonspecific isotype matched antibodies at the same concentration.
FasL Western blot analysis
To perform Western blot analysis for FasL, intact placental villi, 96-h phytohemagglutinin (PHA)/interleukin (IL)-2 activated lymphocytes, ED27 trophoblast cells, or WS1 fetal fibroblasts were homogenized in RIPA buffer (5 mmol Tris, 150 mmol NaCl, 1% Nonidet P-40, 0.5% Na deoxycholate, 0.1% SDS, pH 7.5). The homogenate was clarified by centrifugation, and total protein content of the supernate was determined by a Coomassie protein assay using albumin as the standard (Pierce Chemical Co., Rockford IL). For FasL Western analysis, 50 µg of total cellular protein was fractionated in a denaturing 10% SDS-polyacrylamide gel by electrophoresis. The fractionated protein samples were then transferred to nitrocellulose membranes (Schleicher & Schuell, Inc., Keene, NH), and nonspecific binding was blocked for 2 h in 5% nonfat dry milk in Tris-buffered saline. The membranes were incubated with 0.3 µg/mL of rabbit IgG antibody (Santa Cruz Biotechnology, Inc.) developed against a synthetic FasL peptide that corresponds to the intracellular portion of the FasL molecule, or 0.3 µg/mL of nonspecific rabbit IgG antibody as a control. Development of the Western blots was performed using the ECL system (Amersham, Arlington Heights, IL).
Peripheral blood lymphocyte isolation
To obtain peripheral blood lymphocytes, mononuclear cells were isolated from heparinized peripheral blood from newborn infants (placental cord blood, N = 4) by Histopaque-1077 (Sigma Chemical Co., St. Louis, MO) density centrifugation. The mononuclear cell layer was recovered and washed in RPMI 1640 media (Gibco BRL). The cells were then placed in plastic culture flasks in RPMI with 5% FCS at a concentration of 2 x 106 for 1 h at 37 C, in 5% CO2/air, to allow the monocytes to adhere. The nonadherent lymphocytes were then recovered by gentle rinsing with RPMI 1640, and the adherence procedure was repeated. The nonadherent lymphocytes were then recovered and used for study.
FACS analysis for Fas expression in activated lymphocytes
Isolated lymphocytes were activated by incubation in RPMI 1640 with 10% FCS, 10 µg/mL of phytohemagglutinin (Sigma Chemical Co.), and 10 ng/mL of IL-2 (PharMingen) for 24 h at 37 C in 5% CO2/air. The lymphocytes were then washed and incubated in RPMI 1640 with 10% FCS and 10 ng/mL of IL-2 for an additional 48 h to induce Fas expression, and for 96 h to induce FasL expression (7). For FACS analysis of Fas expression, activated or unactivated lymphocytes were incubated with either 10 µg/mL of fluorescein isothiocyanate (FITC) labeled anti-Fas antibody or FITC-labeled isotype-matched nonspecific antibody control (PharMingen) for 1 h at 4 C. The cells were washed and analyzed for Fas expression using a FACScan flow cytometer (Becton Dickson and Co., Franklin Lakes, NJ).
TUNEL (in situ death) assay for trophoblast-induced lymphocyte apoptosis
ED27 trophoblast cells and WS1 fibroblast cells were grown in 6-well plates in their respective growth media. Once confluent, the media was changed to RPMI 1640 with 10% FCS and either 1 x 105 activated or unactivated lymphocytes was added to the wells (N = 3 for each treatment), resulting in a target:effector cell ratio of approximately 1:20. After 24 h of coculture, the wells were gently rinsed to recover the nonadherent lymphocytes. Cytospin cell preparations of the lymphocytes were fixed in 4% formalin at room temperature for 30 min. After fixation, the slides were washed in PBS and treated with acetic acid:ethanol (1:2) at -20 C for 10 min. The slides were washed in PBS and then blocked with 0.1% BSA for 30 min. The slides were washed once in PBS and then in H2O. The TUNEL reaction mixture (Boehringer Mannheim, Indianapolis, IN) was applied to the slides and then incubated at 37 C for 1 h to label 3' DNA ends with FITC-labeled deoxyuridine 5'-triphosphate. Apoptotic cells were observed under phase and fluorescence microscopy. Three random 200 x microscopic fields per slide were photographed, and the number of positively fluorescing nuclei and the total number of cells were counted. Occasional nonadherent dead trophoblast cells could be readily distinguished morphologically from lymphocytes by their large sized and substantially increased cytoplasmic-to-nuclear ratio. These experiments were performed on lymphocytes isolated from four different individuals, and the results were analyzed by ANOVA for statistical comparisons. To demonstrate the specificity of the FasL-induced apoptosis by trophoblast on activated lymphocytes, 10 µg/mL of neutralizing anti-FasL antibody (NOK-2, PharMingen) or nonspecific control antibody was added to trophoblast/activated lymphocyte coculture experiments to inhibit FasL activity.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
). In addition, extravillous
cytotrophoblast in the chorion of the placental membranes also
localized immunoreactive FasL (Fig. 1C). These are the sites where
fetal tissues would be in contact with the maternal immune system. The
specificity of the antibody staining was verified by the lack of any
specific staining with anti-FasL antibody preabsorbed with FasL peptide
(Fig. 1B) or with nonspecific control antibody (data not shown). Fas
localization was seldom seen in the fetal placental villi but instead
was found in occasional cells of the maternal decidual tissues
(Fig. 1D). The specificity of the Fas antibody staining was verified by
the lack of staining with nonspecific control antibody (Fig. 1E). The
colocalization experiments for Fas and CD45 demonstrated that some of
the Fas-expressing cells in maternal decidua were leukocytes (Fig. 2, A and B). These experiments also
showed that not all CD45 positive cells in decidua expressed Fas, and
not all Fas positive cells expressed CD45. Substitution of the anti-Fas
or anti-CD45 antibodies with nonspecific isotype specific antibody at
the same concentration resulted in no specific staining (Fig. 2, C and
D), demonstrating the specificity of the colocalization staining
procedure.
|
|
, immunoreactive bands for FasL were
seen at 46 kDa in placental villi and the ED27 trophoblast
cell line. These findings are consistent with the localization of FasL
to placental trophoblast by immunohistochemistry shown in Fig. 1
.
Additional immunoreactive bands for FasL were evident at 50 kDa and 29
kDa in placental villi. The WS1 fibroblast cell line, however, did not
demonstrate any immunoreactive FasL. Specificity of the Western blot
analysis was demonstrated by substituting the FasL antibody with
nonspecific rabbit antibody at the same concentration and preabsorbing
the primary anti-FasL antibody with FasL peptide, both of which
abolished the immunoreactive bands. These results have been reproduced
in at least two other separate experiments.
|
). After activation with PHA and IL-2
for 72 h, however, a marked up-regulation of Fas antigen
expression was seen (Fig. 4B) but not FasL (results not shown). When
activated lymphocytes that express Fas were cocultured with
FasL-expressing ED27 trophoblast for 24 h, 30% of the
lymphocytes underwent apoptosis, as determined by the TUNEL assay (Fig. 5B). In these experiments, lymphocyte
apoptosis was caused by ED27 trophoblast cell FasL
activation of Fas expressed on the lymphocytes because apoptosis was
inhibited by 40% with the addition of neutralizing antibody to FasL
(Fig. 6). In addition, coculture of
unactivated non-Fas-expressing lymphocytes with ED27
trophoblast (Fig. 5D) or activated lymphocytes with non-FasL-expressing
WS1 fetal fibroblast cells (Fig. 5F) resulted in only minimal
lymphocyte apoptosis of 4–5%.
|
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The need for local immune tolerance mechanisms at the maternal-fetal interface comes from numerous studies suggesting that the maternal immune system initiates an immune response directed against the fetus. During pregnancy, there is a large influx of macrophages and lymphocytes into the decidua at the maternal-fetal interface. Leukocytes comprise up to 40% of the cells found in decidua during pregnancy (13). Cytokines such as IL-1 and IL-6 are up-regulated in decidua during pregnancy, along with human leukocyte antigen (HLA)-DR (14, 15). Findings of increased leukocytic infiltrates and elevated IL-1 and HLA-DR expression are also found during transplant organ graft rejection (16). Finally, some mothers are known to develop antibodies directed against paternal HLA antigens found in the fetus (16A ), in addition to antibodies directed against the placenta (17). These findings are consistent with a maternal immune response directed toward the fetus.
Given the many different effector arms of the immune system, it is not surprising that a number of mechanisms, other than Fas/FasL, have been described for maternal immune tolerance to the fetus. Central to all of these mechanisms is the fact that maternal immunotolerance during pregnancy is a phenomena mainly localized to the maternal-fetal interface. A primary mechanism for maternal immune tolerance to the fetus is the lack of classic major histocompatibility complex (MHC) antigen expression on trophoblast cells (18). Trophoblast do express a unique major histocompatibility complex (MHC) class I antigen designated HLA-G, but this antigen has very limited polymorphism, does not seem to stimulate T cell activation (19), and inhibits NK cell activity (20). A number of immunosuppressive substances are at the maternal-fetal interface. One of the most potent of these immunosuppressive substances is transforming growth factor-ß (TGF-ß). TGF-ß is a multifunctional peptide with potent immunosuppressive activities, including inhibition of IL-1-induced lymphocyte proliferation, lymphokine-activated killer cell activity, cytotoxic T cell activity, natural killer cell activity, and macrophage cytotoxicity (21, 22, 23, 24). Both the placenta and placental membranes produce significant amounts of bioactive TGF-ß throughout pregnancy (15). Other substances produced by the placenta that can suppress cell-mediated immunity are PGE2, prostacyclin, and progesterone (25, 26, 27). Protection from maternal humoral immunity comes from several mechanisms. The rapid binding and internalization of antibody by Fc receptors on the trophoblast helps remove maternal antibodies which might result in complement fixation or help mediate antibody-dependent cell-mediated cytotoxicity (28). In addition, trophoblast cells express CD59, which is an inhibitor of the complement cascade (29). Taken together, these findings suggest there are multiple mechanisms to prevent maternal immune rejection of the fetus.
Although Fas/FasL probably plays an active role in maternal immunotolerance to the fetus, the absolute necessity of trophoblast FasL expression for maternal immunotolerance of the fetus has not been demonstrated. Mice with nonfunctional mutations of FasL (gld) can reproduce. These mice, however, lack functional FasL, which is expressed on normal mouse trophoblast and is thought to prevent trafficking of maternal activated lymphocytes to the placenta (30). Consequently, gld mice tend to have smaller litters and more fetal resorptions which are associated with placental inflammatory infiltrates. In the absence of a functional Fas/FasL system, other mechanisms for maternal immunotolerance to the fetus are sufficient to prevent absolute pregnancy failure but insufficient to prevent reduced reproductive efficiency. Another function of trophoblast FasL expression could be to reduce the inflammatory response to vaginal bacteria that gain access to the placental membranes through a partially dilated cervix. Both neutrophils and monocytes constitutively express Fas and undergo apoptosis in the presence of FasL (31). Limiting the inflammatory response to bacteria would be beneficial because chorioamnionitis is associated with increased local production of PGs, which can result in uterine contractions and premature labor and delivery.
In conclusion, our findings, demonstrating the expression of FasL on trophoblast at the maternal-fetal interface and the ability of FasL-expressing trophoblast cells to induce apoptosis in activated lymphocytes, may help to identify a mechanism for maternal immunotolerance to the fetus in human pregnancy.
|
Footnotes |
|---|
Received March 19, 1998.
Revised January 28, 1999.
Accepted February 24, 1999.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
, and transforming growth
factor-ß (TGF-ß) expression in endometrium, placenta, and
placental membranes. Am J Obstet Gynecol. 163:1430–1437.[Medline]
, and tumor
necrosis factor) and their relevance to rejection. Transplant Proc. 21:21–30.
chain in human cytotrophoblasts.
In: Chaouat G, Mowbray J, eds. Cellular and molecular biology of the
materno-fetal relationship. London: John Libbey Eurotext Ltd.;212
:21–28.
This article has been cited by other articles:
 |
|
 |
|
  A. Kaponis, A. Skyrlas, N. Zagorianakou, I. Georgiou, V. Passa, E. Paraskevaidis, and G. Makrydimas Coelomic cells show apoptosis via Fas/FasL system: a comparative study between healthy human pregnancies and missed miscarriages Hum. Reprod., May 1, 2008; 23(5): 1159 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Minas, U. Jeschke, S.N. Kalantaridou, D.U. Richter, T. Reimer, I. Mylonas, K. Friese, and A. Makrigiannakis Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin Mol. Hum. Reprod., September 1, 2007; 13(9): 663 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Harris, R. J. Keogh, M. Wareing, P. N. Baker, J. E. Cartwright, J. D. Aplin, and G. S. J. Whitley Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism Am. J. Pathol., November 1, 2006; 169(5): 1863 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Selam, U. A. Kayisli, G. E. Akbas, M. Basar, and A. Arici Regulation of FAS Ligand Expression by Chemokine Ligand 2 in Human Endometrial Cells Biol Reprod, August 1, 2006; 75(2): 203 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Straszewski-Chavez, V. M. Abrahams, and G. Mor The Role of Apoptosis in the Regulation of Trophoblast Survival and Differentiation during Pregnancy Endocr. Rev., December 1, 2005; 26(7): 877 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Wolkersdorfer, C. Marx, J. Brown, S. Schroder, M. Fussel, E. P. Rieber, E. Kuhlisch, G. Ehninger, and S. R. Bornstein Prevalence of HLA-DRB1 Genotype and Altered Fas/Fas Ligand Expression in Adrenocortical Carcinoma J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1768 - 1774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Frangsmyr, V. Baranov, O. Nagaeva, U. Stendahl, L. Kjellberg, and L. Mincheva-Nilsson Cytoplasmic microvesicular form of Fas ligand in human early placenta: switching the tissue immune privilege hypothesis from cellular to vesicular level Mol. Hum. Reprod., January 1, 2005; 11(1): 35 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Ashton, G. St. J. Whitley, P. R. Dash, M. Wareing, I. P. Crocker, P. N. Baker, and J. E. Cartwright Uterine Spiral Artery Remodeling Involves Endothelial Apoptosis Induced by Extravillous Trophoblasts Through Fas/FasL Interactions Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 102 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Straszewski-Chavez, V. M. Abrahams, E. F. Funai, and G. Mor X-linked inhibitor of apoptosis (XIAP) confers human trophoblast cell resistance to Fas-mediated apoptosis Mol. Hum. Reprod., January 1, 2004; 10(1): 33 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Abrahams, S. L. Straszewski-Chavez, S. Guller, and G. Mor First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis Mol. Hum. Reprod., January 1, 2004; 10(1): 55 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. A. Kayisli, B. Selam, O. Guzeloglu-Kayisli, R. Demir, and A. Arici Human Chorionic Gonadotropin Contributes to Maternal Immunotolerance and Endometrial Apoptosis by Regulating Fas-Fas Ligand System J. Immunol., September 1, 2003; 171(5): 2305 - 2313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R Balkundi, J. A Ziegler, J. F Watchko, C. Craven, and M. Trucco Regulation of FasL/Fas in Human Trophoblasts: Possible Implications for Chorioamnionitis Biol Reprod, August 1, 2003; 69(2): 718 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Selam, U. A. Kayisli, J. A. Garcia-Velasco, G. E. Akbas, and A. Arici Regulation of Fas Ligand Expression by IL-8 in Human Endometrium J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3921 - 3927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Aschkenazi, S. Straszewski, K. M.A. Verwer, H. Foellmer, T. Rutherford, and G. Mor Differential Regulation and Function of the Fas/Fas Ligand System in Human Trophoblast Cells Biol Reprod, June 1, 2002; 66(6): 1853 - 1861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Selam, U. A. Kayisli, N. Mulayim, and A. Arici Regulation of Fas Ligand Expression by Estradiol and Progesterone in Human Endometrium Biol Reprod, October 1, 2001; 65(4): 979 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ait-Azzouzene, S. Caucheteux, F. Tchang, J. Wantyghem, R. Moutier, A. Langkopf, M.-C. Gendron, and C. Kanellopoulos-Langevin Transgenic Major Histocompatibility Complex Class I Antigen Expressed in Mouse Trophoblast Affects Maternal Immature B Cells Biol Reprod, August 1, 2001; 65(2): 337 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wongweragiat, R. F. Searle, and J. N. Bulmer Expression of Fas/Fas Ligand by Decidual Leukocytes in Hydatidiform Mole Biol Reprod, March 1, 2001; 64(3): 784 - 789. [Abstract] [Full Text]
|
|
|
|
|
|
V. D. Dixit and N. Parvizi Pregnancy Stimulates Secretion of Adrenocorticotropin and Nitric Oxide from Peripheral Bovine Lymphocytes Biol Reprod, January 1, 2001; 64(1): 242 - 248. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. S. Fedarko, B. Fohr, P. G. Robey, M. F. Young, and L. W. Fisher Factor H Binding to Bone Sialoprotein and Osteopontin Enables Tumor Cell Evasion of Complement-mediated Attack J. Biol. Chem., May 26, 2000; 275(22): 16666 - 16672. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
-square analysis).
The addition of FasL neutralizing antibody (D) at the beginning of the
coculture experiments with activated lymphocytes and ED27
trophoblast resulted in a 40% decrease in lymphocyte apoptosis,
compared with the coculture experiments without the FasL neutralizing
antibody (P < 0.05,