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Biomedical subjects

M W Fanger

Publications and source records attributed to M W Fanger.

At least 55 records · Page 3Linked to original sources
PubMed1991

Human B cells cannot be triggered to kill target cells through their Fc gamma RII or Fc epsilon RII receptors.

There has been some controversy as to whether or not B cells can kill target cells through their Fc receptors. To address this, we have examined the ability of human B cells from a variety of sources to lyse hybridoma cells with specificity for either the B cell Fc gamma RII or Fc epsilon RII using a reverse killing assay, as well as their ability to lyse opsonized chicken erythrocytes using a classic ADCC assay. Tonsil B cells, chronic lymphocytic leukemia B cells, and Epstein-Barr virus-induced B cells, even after preactivation with a cocktail of cytokines, all failed to lyse any of these targets. We conclude that Fc gamma RII and Fc epsilon RII on human B cells are not cytotoxic trigger molecules.

Animals↗
PubMed1991

Bispecific antibodies and targeted cellular cytotoxicity.

The Second International Conference on Bispecific Antibodies (BsAbs) and Targeted Cellular Cytotoxicity considered how targeted cytotoxicity can be used (1) to increase understanding of the general mechanisms of cellular cytotoxicity and (2) clinically in the treatment of cancer and infectious disease. BsAbs, the main mediators of targeted cellular cytotoxicity, can be made by chemical crosslinking, by fusing hybridoma cells and by molecular genetic approaches. BsAbs bind to target cells via one V region and trigger molecules such as T-cell receptors (TCRs) or FcR for IgG (Fc gamma R) on cytotoxic cells via their other V region. This linking of triggering structures to target cells induces target cell lysis and provides important clues to the signals used to elicit the lytic process.

Animals↗
PubMed1990

Evaluation of the antibody-dependent cytotoxic capabilities of individual human monocytes. Role of Fc gamma RI and Fc gamma RII and the effects of cytokines at the single cell level.

In this report we present evidence that not all human peripheral blood monocytes mediate antibody-dependent cellular cytotoxicity (ADCC), and that this function may be determined on an individual cell by both the type and level of expression of FcR, and by the state of cellular activation and/or differentiation. Although the diverse range of effector and regulatory functions performed by human monocytes suggests the possibility of distinct subsets, it is not clear whether observed functional heterogeneity reflects the presence of true monocyte subpopulations, or whether this diversity represents a continuum of maturational states present in the peripheral circulation. In an attempt to address this question, we investigated the ability of human monocytes to carry out ADCC at the single cell level, with emphasis on the role of the three FcR for IgG (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) in mediating cytotoxicity. Using a modified plaque assay, 58.3% +/- 4.9 of freshly isolated monocytes mediated ADCC, as evidenced by the formation of lytic plaques in monolayers of ox erythrocyte (oxE) target cells. Significant increases in the number of plaque-forming cells were observed after positive selection by flow microfluorimetry for those monocytes expressing high levels of Fc gamma RI and Rc gamma RII, but not Fc gamma RIII. Bispecific antibodies composed of Fab fragments of anti-oxE antibody covalently coupled to Fab fragments of anti-Fc gamma R antibodies were used to independently evaluate the ability of Fc gamma RI, Fc gamma RII, and Fc gamma RIII to mediate single cell cytotoxicity. Significant increases in the number of plaque-forming cells were observed in the presence of anti-Fc gamma RI x anti-oxE and anti-Fc gamma RII x anti-oxE bispecific antibodies, confirming the efficiency of Fc gamma RI and Fc gamma RII as cytotoxic trigger molecules on human monocytes. Incubation of monocytes with purified rIFN-gamma and granulocyte macrophage-CSF, but not IL-2, IL-3, IL-4, IL-6, or TNF-alpha, also resulted in significant increases in the number of monocytes mediating cytotoxicity, suggesting that cytotoxic ability at the single cell level may be influenced by factors which effect monocyte activation and differentiation, respectively. Overall, these studies demonstrate that freshly isolated human monocytes are heterogeneous in their ability to mediate ADCC, and suggest that this functional diversity arises not from discrete subpopulations of cells, but from a continuum of maturational/activational states present within the peripheral circulation.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Human alveolar macrophage FcR-mediated cytotoxicity. Heteroantibody- versus conventional antibody-mediated target cell lysis.

Human alveolar macrophage have three distinct receptors for IgG: FcRI, FcRII, and FcRIII. In order to compare the ability of these receptors to mediate target cell lysis, three different assay systems were examined. First, we studied lysis of chicken E (CE) opsonized with heteroantibodies, which are synthetic antibodies composed of Fab fragments with anti-FcR activity covalently linked to Fab fragments with anti-CE activity. We found alveolar macrophage readily lysed heteroantibody-opsonized CE via each of the three FcR classes (FcRI, 20 +/- 5%; FcRII, 27 +/- 7%; and FcRIII, 13 +/- 13%, p less than 0.05). Non-FcR-dependent lysis of anti-beta 2-microglobulin x anti-CE heteroantibody-opsonized CE was not detected. Second, lysis of hybridoma cell lines bearing anti-FcR antibodies on their cell surface was examined to assess killing of "tumor-like" target cells. Whereas peripheral blood monocytes and lymphocytes were able to lyse hybridoma cell lines bearing surface anti-FcR mAb, alveolar macrophages were not. Third, activity of alveolar macrophage FcR was examined in a conventional antibody-dependent cellular cytotoxicity assay by using O+ (R1,R2) human RBC opsonized with human anti-D and anti-CD serum as target cells. We found lysis of anti-D and anti-CD opsonized human RBC was mediated exclusively via FcRI. No activity of FcRII or FcRIII was detected in these latter assays even if performed under conditions that impair FcRI activity. Thus, all three FcR present on alveolar macrophage mediate lysis of heteroantibody-opsonized CE; in contrast, with the use of a conventional antibody-dependent cellular cytotoxicity assay, only FcRI activity was detected. We were unable to demonstrate lysis of anti-FcR-bearing hybridoma cell lines by alveolar macrophages.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

The effect of cytokines on the expression and function of Fc receptors for IgG on human myeloid cells.

We examined expression and cytotoxic triggering capability of the three Fc receptors for IgG (Fc gamma R) on human monocytes, PMNs and myeloid cell lines after in vitro culture with various cytokines. Fc gamma R expression was evaluated using specific anti-Fc gamma R monoclonal antibodies (mAb). The cytotoxic capability of each Fc gamma R was examined after the effector cells were treated with the recombinant cytokines IFN-gamma. TNF alpha, GM-CSF, G-CSF, M-CSF, IL-1, IL-2, IL-3, IL-4, or IL-6. Hybridoma cell lines (HC) bearing antibody directed to Fc gamma RI (HC 32), Fc gamma RII (HC IV.3) or Fc gamma RIII (HC 3G8) were used as targets, as were chicken erythrocytes (CE) sensitized with heteroantibodies composed of anti-Fc gamma R mAbs (32, IV.3, 3G8) linked to anti-CE antibody. Only IFN-gamma treatment significantly increased Fc gamma R expression and then only Fc gamma RI. IFN-gamma dramatically up-regulated Fc gamma RI expression on all cells tested. However, ADCC was enhanced by treatment with a number of cytokines other than IFN-gamma. GM-CSF, TNF, and IFN-gamma treatment enhanced killing of HC 32 and HC IV.3 by in vitro cultured monocytes. G-CSF treatment enabled PMNs to kill HC through Fc gamma RII, whereas PMN killing of HC through Fc gamma RIII could not be induced by any of the cytokines studied. Although only IFN-gamma treatment increased ADCC of CE by monocytes, GM-CSF treatment as well as IFN-gamma treatment augmented ADCC of CE by PMNs. In addition to IFN-gamma treatment, IL-6 treatment enabled U937 cells to lyse CE. Whereas IFN-gamma-treated U937 cells killed CE through both Fc gamma RI and Fc gamma RII, IL-6-treated U937 cells killed CE only through Fc gamma RI. In addition to IFN-gamma treatment, G-CSF treatment enabled HL-60 cells to lyse CE through both Fc gamma RI and Fc gamma RII. These results demonstrate that although IFN-gamma appears unique in regulating Fc gamma R expression on myeloid cells, cytokines other than IFN-gamma affect ADCC by these cells in a receptor-specific manner.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Functional comparison of the inductions of NADPH oxidase activity and Fc gamma RI in IFN gamma-treated U937 cells.

The capacity to generate superoxide anion (O2-) can be induced in U937 cells by various agents known to cause myeloid cell differentiation. Other reported differentiation events include diminished cell proliferation and the induction by gamma-interferon (IFN gamma) of Fc receptors for immunoglobulin G1 (Fc gamma RI). In this study, we differentiated U937 cells and high Fc gamma RI-expression mutants of U937 cells by treating them with IFN gamma. We compared the time courses over which surface Fc gamma RI became maximal, NADPH oxidase activity was induced, and the antiproliferative effect of IFN gamma was detected. Oxidase activity was measured by stimulating cells with PMA or by activating surface Fc gamma RI using aggregated human IgG1 or second antibody crosslinking of mAb 32/Fc gamma RI complexes. We found that IFN gamma in the absence of additional lymphokines induced high levels of oxidase activity in maximally differentiated U937 cells with even higher levels in the fully differentiated high-Fc gamma RI expression mutants (greater than 8 nmoles/10(6) cells/min for A12.13 cells). Over the course of differentiation, maximal induced levels of Fc gamma RI were reached after 1 to 2 days of IFN gamma treatment, prior to the antiproliferative effect of the lymphokine. In contrast, oxidase activity was induced after a lag of approximately 2 days, becoming maximal only after 4 to 6 days of IFN gamma treatment. This comparison of the induction of Fc gamma RI with that of oxidase activity triggered through Fc gamma RI indicated that the rapid increase of surface receptor was not accompanied by a completion of the pathway of Fc gamma RI-mediated oxidase activity. However, the time courses of induction detected by PMA and Fc gamma RI-agonists were coincident suggesting that the development of oxidative capacity could be due to the induction of components required by both the PMA- and surface receptor-mediated pathways. There are several oxidase components that are known to be IFN gamma-inducible, such as the oxidase flavoprotein, a b558 cytochrome peptide, and oxidase-requiring cytosolic components, and it is possible that one or a set of these components could be the limiting factor(s) for IFN gamma-induced oxidase activity.

Antigens, Differentiation↗
PubMed1990

Monocytes and polymorphonuclear neutrophils of patients with streptococcal pharyngitis express increased numbers of type I IgG Fc receptors.

Studies using cultured cells have shown that gamma interferon (IFN-gamma) induces the expression of Fc gamma RI (the type I Fc receptor for IgG) on human polymorphonuclear neutrophils (PMN) and greatly increases the number of these receptors on human monocytes. Administration of rIFN-gamma in vivo also causes enhanced Fc gamma RI expression on these cell populations. Because streptococcal antigens are potent inducers of IFN-gamma in vitro, we postulated that IFN-gamma would be produced endogenously in vivo in patients with streptococcal infections. Such production of IFN-gamma in vivo, even at low levels, might be expected to induce the expression of Fc gamma RI on monocytes and neutrophils. To evaluate this possibility, we used monoclonal antibody 32 (mAb 32), which is specific for Fc gamma RI, to quantitate the expression of this receptor on human peripheral blood cells. We measured the binding of mAb 32 to monocytes and PMNs isolated from healthy donors and from patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis. PMNs from healthy donors (n = 12) had 700 +/- 600 (mean +/- SD) mAb 32 binding sites. Patients with pharyngitis and negative throat culture for GABHS (n = 11) had 2,100 +/- 1,600 sites on their PMNs. In contrast, the PMNs from patients with documented GABHS pharyngitis (n = 12) had 11,600 +/- 7,500 mAb 32 binding sites on their surface. There was a similar change in the expression of Fc gamma RI on monocytes, with control monocytes having a mean of 19,900 +/- 3,200 mAb 32 binding sites per cell and the GABHS-positive monocytes having 47,500 +/- 21,400 sites. The GABHS-negative throat culture group had a slightly elevated number of Fc gamma RI with a mean of 28,200 +/- 8,400 sites. 10 patients with documented urinary tract infections and three patients with uncomplicated pyelonephritis had no elevation in Fc gamma RI expression. These studies demonstrate that a localized group A streptococcal infection can cause systemic activation of the entire circulating pool of phagocytes, and suggest that a similar level of activation is uncommon in localized gram-negative infections of the urinary tract.

Antigens, Differentiation↗
PubMed1990

The prevalence and distribution of macrophages bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in synovium.

Fc-receptors for IgG (Fc gamma R) are important triggers of effector function in macrophages. We have investigated the distribution of cells bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in 14 synovia and 3 nodules from rheumatoid arthritis (RA) patients, using monoclonal antibodies on serial cryostat sections. 8 osteoarthritis (OA), 2 ankylosing spondylitis (AS) patients and one sarcoid patient were also studied. Significant numbers of macrophages bearing Fc gamma R were present in inflamed synovial tissue with no significant difference in relative frequency between RA and OA. There was no correlation with the degree of lymphocytic infiltration. Distinctive staining patterns for the three Fc-receptors suggest differential regulation of these molecules on macrophages in synovium.

Antigens, Differentiation↗
PubMed1989

My 43, a monoclonal antibody that reacts with human myeloid cells inhibits monocyte IgA binding and triggers function.

A mAb My 43 of the IgM isotype was obtained from a fusion of spleen cells immunized against human monocytes. This mAb inhibited monocyte binding of both soluble FITC-labeled IgA and IgA-coated E, whereas it did not inhibit IgG binding. The Ag recognized by My 43 was induced on HL-60 cells in parallel with IgA binding ability by 1-25 dihydroxy-vitamin D3 treatment. Phagocytosis of IgA-coated E by monocytes and 1-25 dihydroxyvitamin D3-treated HL-60 cells was inhibited by My 43. Furthermore, a heteroantibody of My 43 x F(ab)'2 anti-E promoted phagocytic uptake of E by monocytes. Production of superoxide anion by IFN-gamma treated U-937 cells was stimulated by My 43 but not by other IgM mAb recognizing myeloid cells. By these criteria My 43 recognized a molecule capable of triggering function. Moreover, its binding reactivity, ability to block binding of IgA and IgA-complexes, and its ability to induce activation of IgA receptor bearing myeloid cells, are consistent with the possibility that My 43 reacts with the IgA receptor on these cells.

Animals↗
PubMed1989

The mechanisms of antibody-dependent killing mediated by lymphoid and myeloid cells are distinct based on different divalent cation requirements.

To further understand the mechanism(s) of antibody-dependent cell-mediated cytotoxicity (ADCC) by various effector populations, we have examined the extracellular Ca++ and Mg++ requirements for ADCC performed by lymphocytes, monocytes, polymorphonuclear leukocytes and peritoneal macrophages. We have used the anti-Fc gamma R-bearing hybridoma cell lines (HC) as self directed targets for ADCC to analyse the triggering ability of each of the three defined Fc gamma R; Fc gamma RI, Fc gamma RII, and Fc gamma RIII. Lymphocyte killing of the anti-Fc gamma RIII bearing HC (HC 3G8) was Ca++ dependent, but Mg++ independent. In contrast, monocytes and PMN killed the anti-Fc gamma RI- (HC 32) and the anti-Fc gamma RII- (HC IV.3) bearing HC in a Mg++-dependent, Ca++-independent fashion. In addition, freshly prepared monocytes were able to kill HC 3G8 in a Mg++-dependent, Ca++-independent fashion, indicating that low levels of Fc gamma RIII may be functionally detected on monocytes. Peritoneal macrophages were able to kill all three of the anti-Fc gamma R bearing HC in a Mg++-dependent, Ca++-independent fashion. Thus, the same target is lysed by myeloid cells in the presence of Mg++ without Ca++ and by lymphoid cells in the presence of Ca++ without Mg++. These results suggest that at least two distinct mechanisms of ADCC exist that depend on the type of effector cell mediating antibody-dependent killing and not necessarily on the Fc gamma R type triggered.

Antibodies, Monoclonal↗
PubMed1989

Transient activation of the NADPH oxidase through Fc gamma RI. Oxidase deactivation precedes internalization of cross-linked receptors.

It is well known that Fc gamma R mediate the rapid release of agents of inflammation and, in addition, play an important role in the uptake of stimulatory antibody complexes. Activation of the FcR for human IgG1 (Fc gamma RI) on human monocytic cells triggers a transient activation of the NADPH oxidase. In this study, we tested the possibility that transience of the NADPH oxidase activation might have been the result of rapid internalization of cross-linked Fc gamma RI. Stimulatory receptor moieties were formed by cross-linking Fc gamma RI with receptor-specific mAb that are known to trigger superoxide anion release. The formation of the stimulatory receptor units was determined by quantitating the rate of superoxide anion production through its reduction of cytochrome c. This rate has been found to correlate with the rate of binding of cross-linking antibody and, therefore, the rate of formation of the stimulatory moieties (receptor aggregates). Internalization of cross-linked Fc gamma RI was measured by quantitation of cell-associated FITC-labeled Fc gamma RI-specific mAb resistant to acid elution. We found that cross-linking antibody bound to Fc gamma RI continued to be taken up by the cells well after cessation of oxidase activity. The constant rate of uptake and the differential effect of temperature on these two functions suggested that they are separately regulated. Quantitation of cross-linked receptors that were inactive, i.e., no longer stimulating superoxide anion production, indicated that 50% of internalizable, and therefore cross-linked, Fc gamma RI remained on the surface after oxidase activity had ceased. This evidence of cessation of oxidase activity before the endocytic uptake of mAb/R stimulatory units indicates that the activated state of surface cross-linked Fc gamma RI is of brief duration and that occupation of the receptors by cross-linking-ligand does not sustain the activated state of the receptor. Thus, Fc gamma RI-mediated oxidase activation is temporally limited to the formation of the stimulatory receptor moiety.

Ammonium Chloride↗
PubMed1989

Monoclonal antibodies that bind to distinct epitopes on Fc gamma RI are able to trigger receptor function.

The human monocyte and macrophage Fc receptor that binds human IgG with high affinity is a surface glycoprotein with a relative molecular mass of approximately 70 kDa. This receptor (Fc gamma RI) has been partially characterized using mAb 32 which binds outside the Fc binding domain of the receptor, but nonetheless triggers Fc receptor-dependent functions. In this study, we describe the properties of four new antibodies with specificity for Fc gamma RI. Based on additivity and cross-blocking studies, we conclude that two of these antibodies (mAb 22 and 44) define a third epitope which is distinct from the binding sites for both mAb 32 and the Fc portion of human IgG. Each Fc gamma RI-specific hybridoma was selected for stable sublines expressing high levels of mAb on the cell surface, and then tested for the ability of this surface mAb to trigger antibody-dependent cell cytotoxicity. All sublines were killed by human monocytes when used as targets in a 51Cr-release assay, whereas hybridomas specific for myeloid Ag other than Fc gamma RI were not killed. We conclude that Fc receptor function is triggered through binding to each of the three epitopes of Fc gamma RI that we have defined. These mAb will be useful for additional characterization of Fc gamma RI, and may, when incorporated into tumor-directed heteroantibodies, enhance tumor cell killing by human monocytes and macrophages.

Animals↗
PubMed1989

Cross-linking of the high affinity Fc receptor for human immunoglobulin G1 triggers transient activation of NADPH oxidase activity. Continuous oxidase activation requires continuous de novo receptor cross-linking.

Cross-linking of the high affinity Fc receptor for human immunoglobulin G1 (Fc gamma RI) on U937 cells triggered superoxide anion (O-2) release. This was accomplished by the binding of an Fc gamma RI-specific monoclonal antibody, mAb 32, followed by cross-linking of the mAb on the cell with anti-mouse IgG F(ab')2 by Fc gamma RI-specific mAbs 32 and 22 used as an equimolar mixture or by Fc gamma RI-specific mAb 197 (a murine IgG2a and thus a multivalent ligand for Fc gamma RI) alone. At subsaturating concentrations of the Fc gamma RI-cross-linking ligands, O2- generation was continuous over relatively long intervals. However, saturating concentrations triggered an often substantial but always transient O2- burst. This transient burst of oxidase activity ceased with maximal ligand accumulation on the cell. Cells in which oxidase activity had ceased could be restimulated using phorbol 12-myristate 13-acetate or aggregated human IgG1, indicating that cessation of O2- generation was not due to a generalized exhaustion or inhibition of the NADPH oxidase pathway. Cells incubated in subsaturating concentrations of cross-linking antibodies continued to release O2- until binding of the ligand ceased. In addition, the rates of O2- production and ligand accumulation were the same. Thus, continuous O2- production appeared to be dependent upon continuous de novo formation of cross-linked and activated Fc gamma RI. Furthermore, the mol of O2- released in response to Fc gamma RI cross-linking by the multivalent ligand mAb 197 were directly proportional to the mol of mAb bound over a range of saturating and subsaturating concentrations. This evidence suggests a quantal relationship between each Fc gamma RI activated (cross-linked) and the resultant oxidase activity and supports a "rate" model for the activation of this response. Thus, each Fc gamma RI entering the pool of activated receptors probably makes a unitary contribution to the signal. An additional finding showed that cross-linked Fc gamma RI became associated with the cell cytoskeleton and that this association was also transient. Dissociation of Fc gamma RI from its cytoskeletal attachment occurred well after cessation of O2- production.

Animals↗
PubMed1989

Fc gamma R-mediated killing by eosinophils.

In this report we present data on the ability of the different Fc gamma R present on eosinophils to mediate killing of erythroid and tumor targets, and on a comparison of eosinophil and neutrophil Fc gamma R-mediated killing. Erythroid target killing was assessed using chicken erythrocytes (CE) and heteroantibodies composed of Fab fragments of anti-CE antibodies covalently coupled to Fab fragments of anti-Fc gamma R antibodies. Such anti-CE x anti-Fc gamma R reagents permit linkage of CE target cells with the FcR molecules on the eosinophil or neutrophil effector cells. Tumor target killing was assessed using hybridoma cell lines (HC) bearing anti-Fc gamma R antibodies on their cell surface. Freshly isolated eosinophils and neutrophils constitutively express similar amounts of the low affinity Fc gamma R, Fc gamma RII on their cell surface, but neither cell type expresses the high affinity Fc gamma R, Fc gamma RI. In contrast, eosinophils have only about 5% as much of the low affinity Fc gamma R found on human granulocytes and large granular lymphocytes (Fc gamma RIII) as neutrophils. Untreated, freshly prepared eosinophils or neutrophils did not lyse any of the anti-Fc gamma R bearing HC nor did they lyse CE in the presence of anti-Fc gamma R containing heteroantibodies. Upon treatment with granulocyte monocyte-CSF (GM-CSF), both cell types lysed HC-bearing antibody to Fc gamma RII (HC IV.3A) and CE in the presence of anti-CE x anti-Fc gamma RII heteroantibodies. However, neither cell type lysed HC-bearing antibody to Fc gamma RI or Fc gamma RIII, or CE in the presence of anti-CE x anti-Fc gamma RI HA. Treatment with GM-CSF did not significantly alter the number of Fc gamma R on either cell type. Treatment of neutrophils with IFN-gamma for 18 h induced the expression of Fc gamma RI on these cells and their ability to lyse anti-Fc gamma RI- or Fc gamma RII-bearing HC and CE through Fc gamma RI, Fc gamma RII, and Fc gamma RIII. In contrast, 6-h treatment of eosinophils or neutrophils with IFN-gamma induced neither Fc gamma RI expression on either cell type nor killing of HC or CE through Fc gamma R. In summary, incubation with GM-CSF, induced eosinophils and neutrophils to kill anti-Fc gamma RII-bearing HC and to lyse CE through Fc gamma RII. This augmented killing was not associated with enhanced expression of Fc gamma RII.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Monoclonal antibodies identify three IgG Fc receptors in normal human central nervous system.

Functional Fc receptors have been described in the central nervous system (CNS) in the subependymal periventricular regions, leptomeninges, including brain perivascular tissues, and choroid plexus. The distribution of this receptor activity suggests a role in protection of adjacent nervous tissue from IgG-opsonized antigens, including microorganisms. In this report, we have utilized monoclonal antibodies to human Fc gamma RI, II, and III; 32, IV.3, and 3G8, respectively, to immunohistochemically examine the distribution of these receptors in the CNS. Fc gamma RI was only occasionally present in the CNS where it was identified most often in the choroid plexus. Fc gamma RII was the predominant receptor in brain. It as consistently present in leptomeninges, including brain perivascular regions, arachnoid granulations, and choroid plexus stroma. Some samples of subependymal periventricular tissue also displayed Fc gamma RII. Fc gamma RIII was only identified in subependymal periventricular tissue but not in choroid plexus and arachnoid. These results demonstrate that regions of normal adult brain which produce cerebral spinal fluid (CSF) and border on CSF and vascular compartments display Fc gamma R heterogeneity consistent with that of blood monocytes and systemic macrophages.

Aged↗
PubMed1989

The functional properties of Fc gamma RI, II and III on myeloid cells: a comparative study of killing of erythrocytes and tumor cells mediated through the different Fc receptors.

Three distinct Fc receptors for IgG, Fc gamma RI, Fc gamma RII and Fc gamma RIII are known to be associated with human myeloid cells. Using mAb specific for these receptors, and the hydridoma cells lines that produce these mAb, we have examined the ability of each of these receptors on different myeloid cells and cell lines to mediate killing of tumor and red cell targets. Hybridoma cells (HC) expressing anti-Fc gamma RI, Fc gamma RII or Fc gamma RIII upon their surface were used as model self-directed tumor targets. Chicken erythrocytes (CE) were used as another type of target cell and in this case effector cell cytotoxicity was mediated by heteroantibodies (HA) composed of Fab fragments of anti-Fc gamma R mAb covalently linked to Fab fragments of rabbit anti-CE antibodies. Monocytes, lymphocytes, polymorphonuclear cells (PMNs) and the myeloid cell lines U937, HL-60 and THP-1 were used as effector cells either in their native state or after activation with rIFN-gamma. Direct comparison of cytotoxicity by the same effector cell population against both tumor and erythroid targets has permitted definitive evaluation of the ability of the different Fc gamma R to promote cytolysis under two different conditions. Monocytes were able to utilize Fc gamma RI, Fc gamma RII and Fc gamma RIII in killing both CE and HC targets, and incubation with rIFN-gamma augmented their ability to kill CE, particularly through Fc gamma RI. Fc gamma RII and Fc gamma RIII mediated killing of CE by untreated neutrophils. rIFN-gamma induced PMNs to express Fc gamma RI and to mediate killing of CE through this receptor. Moreover, HC targets were not lyzed by untreated neutrophils, but rIFN-gamma activated neutrophils killed HC bearing surface anti-Fc gamma RI and anti-Fc gamma RII, but not anti-Fc gamma RIII. Myeloid cell lines HL-60 and U937 were unable to perform cytotoxicity without prior culture with rIFN-gamma, following which they killed CE through Fc gamma RI and Fc gamma RII, but were still incapable of HC lysis. THP-1, another myeloid cell line, was cytotoxic to CE through Fc gamma RI and Fc gamma RII without activation. Following rIFN-gamma treatment, cytotoxicity through these two Fc gamma R increased and was also mediated by Fc gamma RIII but these cells were still unable to kill HC.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibody-Dependent Cell Cytotoxicity↗