scholarly journals Inhibition of cell growth by monoclonal anti-transferrin receptor antibodies.

1985 ◽  
Vol 5 (8) ◽  
pp. 1814-1821 ◽  
Author(s):  
J F Lesley ◽  
R J Schulte

Five anti-murine transferrin receptor monoclonal antibodies have been characterized with respect to immunoglobulin class, effects on binding of transferrin, and effects on AKR1 lymphoma cell growth in vitro. The immunoglobulin M (IgM) antibodies, but not the IgG antibodies, prevent cell growth. We suggest that the profound effects of the IgM antibodies on cell growth are probably due to extensive cross-linking of cell surface receptors. In support of this, we are able to mimic the growth-inhibiting effects of the IgM antibodies by adding antiimmunoglobulin to an IgG antibody. By flow microfluorimetry, we show that an IgG antibody by itself induces up to a 10-fold downward regulation in the cell surface transferrin receptor, which is accompanied by accelerated receptor degradation. A similar downward regulation is seen in mutant cells resistant to growth inhibition by an IgM antibody, when grown in the selecting antibody. Wild-type cells grown in the presence of IgM antibody do not show receptor downward regulation. Inhibitory effects of antibody plus antiimmuoglobulin on mutant cells are also consistent with extensive cross-linking causing inhibition of growth.

1985 ◽  
Vol 5 (8) ◽  
pp. 1814-1821
Author(s):  
J F Lesley ◽  
R J Schulte

Five anti-murine transferrin receptor monoclonal antibodies have been characterized with respect to immunoglobulin class, effects on binding of transferrin, and effects on AKR1 lymphoma cell growth in vitro. The immunoglobulin M (IgM) antibodies, but not the IgG antibodies, prevent cell growth. We suggest that the profound effects of the IgM antibodies on cell growth are probably due to extensive cross-linking of cell surface receptors. In support of this, we are able to mimic the growth-inhibiting effects of the IgM antibodies by adding antiimmunoglobulin to an IgG antibody. By flow microfluorimetry, we show that an IgG antibody by itself induces up to a 10-fold downward regulation in the cell surface transferrin receptor, which is accompanied by accelerated receptor degradation. A similar downward regulation is seen in mutant cells resistant to growth inhibition by an IgM antibody, when grown in the selecting antibody. Wild-type cells grown in the presence of IgM antibody do not show receptor downward regulation. Inhibitory effects of antibody plus antiimmuoglobulin on mutant cells are also consistent with extensive cross-linking causing inhibition of growth.


2020 ◽  
Vol 58 (6) ◽  
pp. 774-778 ◽  
Author(s):  
Joshua Malo ◽  
Eric Holbrook ◽  
Tirdad Zangeneh ◽  
Chris Strawter ◽  
Eyal Oren ◽  
...  

Abstract Coccidioidomycosis is a common cause of community-acquired pneumonia in endemic areas of the southwestern United States. Clinical presentations range from self-limited disease to severe, disseminated disease. As such, early and accurate diagnosis is essential to ensure appropriate treatment and monitoring. Currently available diagnostic testing has variable accuracy, particularly in certain patient populations, and new tests may offer improved accuracy for the diagnosis of coccidioidomycosis. Serum samples from patients with coccidioidomycosis and controls were tested for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies using the MVista Coccidioides antibody detection EIA and two commonly used commercial enzyme immunoassay (EIA) kits: the IMMY Omega EIA and the Meridian Premier EIA. The sensitivity of the IgG antibody detection was 87.4% using the MVista test compared to 46.6% for IMMY and 70.9% for Meridian. The sensitivity for IgM antibody detection was 61.2% for the MVista test, 22.3% for IMMY and 29.1% for Meridian. For IgG antibody detection, specificity was 90% for the MVista EIA, 94.6% for IMMY, 96.4% for Meridian. For IgM antibody detection, specificity was 95.3% for the MVista test 98.2% for IMMY and 99.1% for Meridian. The MVista Coccidioides antibody EIA offers improved sensitivity, including among high-risk patient populations, for the detection of IgG and IgM antibodies in comparison to other currently available EIAs.


1974 ◽  
Vol 73 (1) ◽  
pp. 127-141 ◽  
Author(s):  
J. E. Cradock-Watson ◽  
Helen Macdonald ◽  
Margaret K. S. Ridehalgh ◽  
M. S. Bourne ◽  
Elise M. Vandervelde

SUMMARYThe indirect immunofluorescent technique has been used to study the specific immunoglobulin responses in the sera of 63 non-immune adult women who received either Cendehill rubella vaccine subcutaneously, RA27/3 rubella vaccine subcutaneously, or RA27/3 vaccine intranasally. IgG, IgA and IgM antibodies increased virtually simultaneously, starting about 2 weeks after vaccination. IgG antibody appeared in all subjects and reached maximum titres 4–6 weeks after vaccination. The mean IgG titres elicited by the three different methods of vaccination did not differ significantly. IgA and IgM antibodies reached their highest titres between 21 and 28 days after vaccination and then declined to low or undetectable titres within about 9 weeks. The maximum IgA titres observed after intranasal administration of RA27/3 vaccine were significantly higher than those which occurred when the same vaccine was given subcutaneously, but no significant difference in IgM titres was observed. When unfractionated sera were examined IgA antibody was detected in 57 cases (91%) and IgM in 51 (81%). Fluorescent examination of fractions obtained by centrifugation on sucrose density gradients frequently revealed small amounts of IgA and IgM antibody which could not be detected by staining unfractionated serum, and with the inclusion of these results IgA antibody was detected in 61 cases (97%) and IgM in 59 (94%).When 39 adults with pre-existing serum antibody were challenged with vaccine a definite IgA response was detected in only one subject and in no case was there any evidence of the appearance of IgM antibody.Nasal antibody, consisting of IgG or IgA or both, was detected in 17 out of 23 non-immune subjects (74%) who received RA27/3 vaccine, either subcutaneously or intranasally. Titres were much lower than those which occur in the natural disease and there was no evidence that nasal antibody was elicited more readily by intranasal than by subcutaneous vaccination.


2000 ◽  
Vol 148 (4) ◽  
pp. 825-838 ◽  
Author(s):  
Sergey S. Akimov ◽  
Dmitry Krylov ◽  
Laurie F. Fleischman ◽  
Alexey M. Belkin

The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.


2021 ◽  
Author(s):  
K.C. Liew ◽  
Chelsea Nguyen ◽  
Nilakshi T Waidyatillake ◽  
John Stenos ◽  
Aaron Walton ◽  
...  

ABSTRACTWhipple’s disease (WD) is a rare infection due to Tropheryma whipplei. Following in-vitro cultivation of T. whipplei, an indirect-immunofluorescence serological assay (IFA) was developed. We tested the hypothesis that this assay could be used to either identify WD patients, or rule out WD, in patients in whom the diagnosis is being considered, based on the antibody titers of their IgM and IgG antibody responses. In this small study fourteen WD patients and 22 healthy volunteers’ sera were obtained from across Australia. All specimens were coded and de-identified before testing. A patient with an IgG antibody titer of ≤1:16 may have WD [sensitivity 57% (8/14) and specificity close to 100% (22/22)]. High IgM antibody titers (≥1:256) were more common in WD patients [sensitivity 50% (7/14) and specificity 86% (19/22)] than in controls. The area under Receiver-Operator-Characteristic curve for IgG in the IFA assay was 0.84 (95% CI 0.69-1.00). At an IgG antibody titer of ≤1:16 the Youden’s index was 0.57. WD patients’ under-produce IgG antibody to T.whipplei but are more likely to over-produce IgM antibodies. This screening IFA serological assay may be clinically useful in detecting those with a possible diagnosis of WD. Patients with an IgG antibody titer of ≤1:16 and an IgM antibody titer of ≥1:256 may have WD and should proceed to a tissue biopsy and PCR for confirmation. Further validation of this assay, by increasing the sample size, by testing it in patients with non-WD disease and trialing in other countries should be undertaken.


1972 ◽  
Vol 70 (3) ◽  
pp. 473-485 ◽  
Author(s):  
J. E. Cradock-Watson ◽  
M. S. Bourne ◽  
Elise M. Vandervelde

SUMMARYThe indirect immunofluorescent technique has been used to study the specific immunoglobulin responses in twelve adult cases of acute uncomplicated rubella. IgG, IgA and IgM antibodies increased virtually simultaneously. IgG antibody persisted throughout the period of study but showed a slight tendency to fall in titre after 7 months. IgM antibody was detected in nine cases. In these patients it was present in high titre 5–15 days after the rash but was not detected after 20 days. IgA antibody was detected in all cases. It was present in high titre 5–20 days after the rash but was no longer detectable after 29 days except in one patient who had a very low titre at 78 days. The presence of specific IgA and IgM indicates recent rubella in uncomplicated cases, and if the immunofluorescent method is used both types of antibody should be sought.


1974 ◽  
Vol 140 (1) ◽  
pp. 239-252 ◽  
Author(s):  
Tomio Tada ◽  
Toshitada Takemori

Passively transferred thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) exerted differential suppressive effect on IgM and IgG antibody responses of syngeneic recipients immunized with DNP-KLH depending primarily on the time when KLH-primed cells were transferred. This was demonstrated by the decrease in the numbers of DNP-specific direct and indirect PFC in the spleen of the recipients given KLH-primed cells at different times during primary and secondary immunization. Whereas the cell transfer simultaneously with or 2 days after the primary immunization produced only slight suppression of the peak IgM antibody response, it caused profound suppression of late IgM and IgG antibody responses. By contrast, the cell transfer 3 days after the immunization produced immediate suppression of the ongoing IgM antibody response resulting in its earlier termination, while being unable to prevent the induction of IgG antibody response. KLH-primed cells could moderately suppress the secondary anti-DNP antibody response, in which IgG antibody response was found to be slightly more sensitive than IgM antibody response to the suppressive influence of KLH-primed cells. The suppressive effect of the KLH-primed spleen cells was completely eliminated by the in vitro treatment of the cells with anti-θ and C before cell transfer, indicating that cells responsible for the suppression are, in fact, T cells. The suppression of DNP-specific antibody response by KLH-primed T cells was achieved only if the recipients were immunized with DNP-KLH but not with DNP-heterologous carrier, suggesting that direct interaction between T and B cells is necessary for the suppression of the antibody response. It is concluded that susceptibility of B cells to the specific suppressive influence of T cells is inherently different depending on the differentiation stage of B cells and on the immunoglobulin class they are destined to produce.


1989 ◽  
Vol 108 (5) ◽  
pp. 1979-1985 ◽  
Author(s):  
F F Roossien ◽  
D de Rijk ◽  
A Bikker ◽  
E Roos

Lymphocyte function-associated antigen-1 (LFA-1) is a leukocyte and lymphoma cell surface protein that promotes intercellular adhesion. We have previously shown that the invasion of hepatocyte cultures by lymphoma cells is inhibited by anti-LFA-1 antibodies (Roos, E., and F. F. Roossien. 1987. J. Cell Biol. 105:553-559). In addition, we now report that LFA-1 is also involved in invasion of lymphoma cells into fibroblast monolayers. To investigate the role of LFA-1 in metastasis of these lymphoma cells, we have generated mutants that are deficient in LFA-1 cell surface expression because of impaired synthesis of either the alpha or beta subunit precursor of LFA-1. We identified at least three distinct mutant clones. The invasive potential of the mutant cells in vitro, in both hepatocyte and fibroblast cultures, was considerably lower than that of parental cells. The metastatic potential of the mutants was much reduced, indicating that LFA-1 expression is required for efficient metastasis formation by certain lymphoma cells.


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