Studies in acute leukemia. I. Antibody-dependent and spontaneous cellular cytotoxicity by leukemic blasts from patients with acute nonlymphoid leukemia.

Leukemic blasts from patients with acute nonlymphoid leukemia were examined for the presence of Ig, receptors for IgGFc, and for their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) against chicken red blood cells (RBC) coated with IgG and spontaneous cell-mediated cytotoxicity (SCMC) against cells of K562 cell line. Leukemic blasts from acute myeloblastic leukemia (AML) patients lacked both Fc receptors and Ig on their surface, had no SCMC activity and majority, but not all of them, lacked ADCC activity. Leukemic blasts from patients with acute monocytic leukemia (AMOL) had Fc receptors, and 50% had IgG on their surface. IgG was cytophilic and appeared not to be directed against cell-surface antigens. This antibody did not interfere with the ADCC activity of leukemic cells. Leukemic blasts from majority of patients with AMOL mediated ADCC, but had no SCMC activity. An association between ADCC and presence of Fc receptor was observed.     

Colony-stimulating factor enhancement of myeloid effector cell cytotoxicity towards neuroectodermal tumour cells

Summary. We conducted experiments to determine the optimal conditions for colony-stimulating factor-enhanced neutrophil- and mononuclear phagocyte-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) using monoclonal antibodies to disialogangliosides expressed on neuroectodermal tumour target cells. Neutrophil ADCC was most effective at effector: target ratios of 100:1, with maximal cytotoxic responses to melanoma target cells generated by 3 h. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) were the most potent stimulators of neutrophil ADCC, and enhanced ADCC activity was inhibited in the presence of antibody to Fc receptor type II (FcRII). GM-CSF and macrophage colony-stimulating factor (M-CSF) treatment of freshly isolated monocytes inhibited antibody-independent cytotoxicity but enhanced antibody-dependent responses. After 3 d in culture with CSF, 3–10-fold enhancement of ADCC against melanoma target cells was observed at effector: target cell ratios of 10:1. Greatest stimulation of macrophage ADCC was obtained when GM-CSF, M-CSF or interleukin 3 (IL-3) were used in conjunction with a secondary stimulus. Although gamma interferon (γ-IFN) did not augment the cytotoxic capability of GM-CSF- and IL-3-stimulated macrophages, prominent cytotoxic enhancement was seen when M-CSF-stimulated macrophages were exposed to γ-IFN. A chimaeric mouse/human monoclonal antibody was found to be equivalent in activity to the murine antibody in neutrophil ADCC; however, in macrophage ADCC assays with submaximal effector cell stimulation, the chimaeric antibody was associated with a two-fold greater response. These studies indicate that under specific conditions, CSFs capable of increasing the number and functional activity of mature myeloid effector cells enhance antibody-dependent cytotoxicity to neuroectodermal tumour target cells.     

Antibody-dependent cellular cytotoxicity of Trypanosoma theileri mediated by purified bovine isotypes and subisotypes

Summary Bovine neutrophils, eosinophils and macrophages mediated in vitro cytotoxicity against Trypanosoma theileri in the presence of purified IgM, IgGl and IgG2 from immune bovine serum. When the immunoglobulin fractions were assayed at similar concentrations, IgM was the most effective isotype mediating killing with all three effector cell types. Using the ELISA with monospecific antisera against the different bovine isotypes and subisotypes, IgM was shown to be contaminated by < 1%. The addition of 0·08 M 2-mercaptoethanol inhibited IgM-mediated ADCC but not that of IgGl or IgG2, and the cytotoxicity occurred in the absence of complement. The presence of isotype and subisotype specific Fc receptors on the bovine effector cells was investigated using a totally homologous erythrocyte-antibody (EA) resetting technique. FC receptors for bovine IgM, IgG1 and IgG2 were detected on bovine neutrophils. Very few FcM receptors were detected on either eosinophils or macrophages, but FcG2 receptors were detected on both cell types, and FcG1 receptors on macrophages. However, eosinophils showed very few FcG1 receptors. The failure to detect all types of Fc receptor on the three different effector cells is discussed.     

Characteristics of Different Rhesus Alloantibodies in Lymphocyte Dependent (K Cell) Cytotoxicity to Human Erythrocytes

The property of rhesus alloantibodies to elicit antibody-dependent, cell-mediated cytotoxicity (ADCC) against target erythrocytes carrying various Rh genotypes was studied. The killer activity of normal peripheral lymphocytes on human erythrocyte target cells carrying the appropriate antigens elicited by alloantisera was measured by 51Cr release at 18 h. There was no correlation between ADCC and antibodies directed to the antigens present on the surface of different genotypes of Rh-positive red blood cells. The agglutinin titre of different Rh antibodies showed no correlation with the level of ADCC although the degree of cellular cytotoxicity was different with different anti-D sera. Anti-C + D+ E antibody caused higher ADCC than anti-C + D and the lowest cytotoxicity was observed with anti-D and anti-D+ E. This raised the possibility that ADCC was elicited by antibodies directed to other specificities. K cell lysis of human red cells by human peripheral blood lymphocytes in vitro suggests that a similar mechanism may operate in vitro in the destruction of erythrocytes coated by allo or autoantibodies.     

The binding of monomeric IgG to human blood monocytes and alveolar macrophages

Macrophage receptor sites for IgG are important in the immune clearance of particles both from the blood and lung. We studied the number, affinity, and density of binding sites for monomeric IgG on human blood monocytes and alveolar macrophages. Monocytes and alveolar macrophages had a similar affinity for monomeric IgG at 37 degrees and 4 degrees C. The half-time for dissociation of the IgG-receptor complex was also similar for both cells. However, alveolar macrophages expressed approximately 5-fold more IgG binding sites than monocytes at both 37 degrees and 4 degrees C. Nevertheless, when cell surface area was estimated, these cells expressed a similar density of IgG binding sites (monocytes = 110 +/- 14.8 IgG binding sites/square micron; pulmonary macrophages = 138 +/- 46.9 IgG binding sites/square micron; p greater than 0.50). Gamma interferon increased the number and density of monocyte binding sites for monomeric IgG by 162 +/- 89%. Furthermore, patients with sarcoidosis, a disorder in which gamma interferon is spontaneously elaborated, expressed a similar increase in the number of IgG binding sites per monocyte, from 24,968 +/- 1,361 for normal subjects to 44,860 +/- 6,652 for patients with sarcoidosis. However, alveolar macrophages from 5 patients with sarcoidosis expressed a normal number of IgG binding sites. These data suggest that there is no major alteration in the Fc(IgG) receptor as monocytes differentiate into alveolar macrophages. Both gamma interferon treatment and sarcoidosis are associated with enhanced expression of the Fc(IgG) receptor on monocytes.     

Characterization of antibody-dependent cytotoxicity mediated by human alveolar macrophages

Antibody-dependent cellular cytotoxicity is believed to be an important host defense mechanism. Although this reaction has been shown to be mediated by various Fc receptor-bearing effector cells, the ability of a mature macrophage population to mediate this reaction has not been previously demonstrated. In this study, alveolar macrophages obtained from normal subjects by subsegmental lung lavage were used to determine whether this mature macrophage population had the ability to mediate antibody-dependent cell killing. The results of this study demonstrated that alveolar macrophages clearly mediate antibody-dependent cellular cytotoxicity against antibody-coated erythrocyte targets and that the kinetics of the reaction are characteristic of an enzyme-substrate interaction. Furthermore, this study demonstrated that alveolar macrophages are more efficient at mediating antibody-dependent cytotoxicity than is their precursor cell, the peripheral blood monocyte.     

In vitro Functional Activity of IgG1 and IgG3 Polyclonal and Monoclonal anti-D

Background and objectives: IgG anti-D is generally restricted to IgG1 and IgG3; it mediates red cell destruction through interactions with IgG Fc receptors (FcγR) on effector cells. The relative ability of these two IgG subclasses of anti-D to mediate haemolysis in vitro by monocytes and K cells was investigated. Materials and methods: Anti-D was affinity purified from 5 preparations of prophylactic anti-D immunoglobulin, and IgG subclasses quantified by ELISA; mean levels were 86.5% IgG1, 1.4% IgG2, 11.6% IgG3 and 0.4% IgG4. IgG1 and IgG3 polyclonal anti-D were further purified separately from some of the anti-D by removal of either IgG3 using magnetic beads coated with anti-IgG3, or of IgG1 using protein A. These preparations were compared with monoclonal anti-D (BRAD-3 and BRAD-5) for their ability to lyse red cells in antibody-dependent cell-mediated cytotoxicity (ADCC) assays. Results: Monocyte-mediated lysis of red cells coated with IgG3 anti-D was approximately twice that of cells coated with IgG1 anti-D at similar sensitization levels, and anti-D preparations containing 10% or more IgG3 gave similar lysis. By contrast, in the K cell ADCC, IgG1 anti-D was 2–4 times more haemolytic than IgG3 anti-D. Polyclonal IgG1 and IgG3 anti-D promoted about 20% more lysis than BRAD-5 (IgG1) and BRAD-3 (IgG3), respectively, in the K cell ADCC, although no difference was observed between polyclonal and monoclonal anti-D in the monocyte ADCC. Conclusions: These experiments demonstrated a functional dichotomy between these two subclasses of anti-D; IgG3-coated red cells were lysed preferentially by monocytes mediated predominantly through FcγRI interactions, whereas haemolysis of IgG1-sensitized cells was mediated mainly by FcγRIII on K cells.     

Receptor-mediated O2- release by alveolar macrophages and peripheral blood monocytes from smokers and nonsmokers. Priming and triggering effects of monomeric IgG, concanavalin A, N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, and cytochalasin D

Receptor-mediated superoxide (O2-) release by alveolar macrophages and peripheral blood monocytes from smokers and nonsmokers was studied in vitro. When the cells were incubated with monomeric IgG or monomeric Fc(IgG) fragment, no cell O2- release was observed. However, when cytochalasin D (Cyto D) was subsequently added to the cell suspension, we observed a markedly enhanced O2- release. Neither Cyto D alone nor the double stimulation of following Cyto D with monomeric IgG induced O2- release. Concanavalin A (Con A) also had a priming effect on O2 release in combination with Cyto D, as did monomeric IgG or monomeric Fc(IgG) fragment. On the other hand, heat-aggregated IgG, N-formyl-methionyl-leucyl-phenylalanine (FMLP), or phorbol myristate acetate (PMA) induced O2- release without the addition of Cyto D. Thus, we observed 2 different mechanisms in the receptor-mediated O2- release by alveolar macrophages and peripheral blood monocytes. Alveolar macrophages from smokers, which had a higher affinity and a larger number of monomeric IgG binding sites per cell than those from nonsmokers, were more reactive to the double stimulation of following monomeric IgG with Cyto D than to that of Con A and Cyto D, FMLP, or PMA, but for peripheral blood monocytes it was the reverse. We conclude that the binding of monomeric IgG to the Fc(IgG) receptor of alveolar macrophages or peripheral blood monocytes results in a priming effect on the cells for O2- release, and that the regulation of receptor-mediated O2- release by alveolar macrophages differs at least in part from that of peripheral blood monocytes.     

Abatacept binds to the Fc receptor CD64 but does not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity

OBJECTIVE: To assess the ability of abatacept to mediate complement-dependent cytotoxicity (CDC) or antibody-dependent cellular cytotoxicity (ADCC) of antigen-presenting cells, and to characterize the binding of abatacept to the 3 Fc receptor classes. METHODS: CDC was measured in vitro using rabbit, baby rabbit, guinea pig, or human complement with human B cell line PM-LCL as the target. ADCC was also measured with PM-LCL target cells, but with human peripheral blood mononuclear cells from 12 healthy blood donors as effectors. Fc receptor binding was analyzed in vitro by flow cytometry and surface plasmon resonance (SPR). RESULTS: In contrast to unmodified CTLA4-Ig, abatacept did not mediate CDC or ADCC of target B cells. While abatacept was found to bind its target receptor, CD80/86, it did not appreciably bind the low-affinity Fc receptors CD16 and CD32 as measured by flow cytometry and SPR. Abatacept was found to minimally bind the high-affinity Fc receptor CD69 as measured by flow cytometry and SPR with a Kd of 3 X 10-7 M as measured by SPR. CONCLUSION: Abatacept does not mediate CDC or ADCC of target B cells in vitro and has limited Fc receptor binding. These data support the concept that abatacept therapeutic activity is primarily due to the binding to CD80/86 through the CTLA4 extracellular domain and not through activities mediated by the modified Fc domain.     

Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells

Glycosylation of the antibody Fc fragment is essential for Fc receptor-mediated activity. Carbohydrate heterogeneity is known to modulate the activity of effector cells in the blood, in which fucosylation particularly affects NK cell-mediated killing. Here, we investigated how the glycosylation profile of 2F8, a human IgG(1) monoclonal antibody against epidermal growth factor receptor in clinical development, impacted effector function. Various 2F8 batches differing in fucosylation, galactosylation, and sialylation of the complex-type oligosaccharides in the Fc fragment were investigated. Our results confirmed that low fucose levels enhance mononuclear cell-mediated antibody-mediated cellular cytotoxicity (ADCC). In contrast, polymorphonuclear cells were found to preferentially kill via high-fucosylated antibody. Whole blood ADCC assays, containing both types of effector cells, revealed little differences in tumor cell killing between both batches. Significantly, however, high-fucose antibody induced superior ADCC in blood from granulocyte colony-stimulating factor-primed donors containing higher numbers of activated polymorphonuclear cells. In conclusion, our data demonstrated for the first time that lack of fucose does not generally increase the ADCC activity of therapeutic antibodies and that the impact of Fc glycosylation on ADCC is critically dependent on the recruited effector cell type.     

Analysis in human neonates of defective antibody-dependent cellular cytotoxicity and natural killer cytotoxicity to herpes simplex virus-infected cells

Human neonatal mononuclear cells (MCs) had low antibody-dependent cellular cytotoxicity (ADCC) compared with cells from adults in a chromium-release assay against Chang liver cells infected with herpes simplex virus (HSV). Polymorphonuclear leukocyte (PMNL) ADCC of neonates was similar to that of adults. In a single-cell agarose conjugation assay IgG antibody to HSV significantly increased conjugation by adult MCs, adult PMNLs, and cord blood PMNLs but not by cord blood MCs. Expression of the high-affinity IgG Fc receptor (FcR) assayed by erythrocyte-antibody rosetting revealed significant differences between adult MC FcR and cord blood FcR. There was no difference in PMNL FcR expression. Human interferon-alpha increased neonatal MC adhesion in the presence of IgG and FcR expression, but it had no effect on MC ADCC. Defective FcR expression and target cell adhesion may partly explain low neonatal MC ADCC. In addition, cord blood cells have a lytic or recycle, as well as an adherence, defect.     

Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function

HM1.24, an immunologic target for multiple myeloma (MM) cells, has not been effectively targeted with therapeutic monoclonal antibodies (mAbs). In this study, we investigated in vitro and in vivo anti-MM activities of XmAb5592, a humanized anti-HM1.24 mAb with Fc-domain engineered to significantly enhance FcγR binding and associated immune effector functions. XmAb5592 increased antibody-dependent cellular cytotoxicity (ADCC) several fold relative to the anti-HM1.24 IgG1 analog against both MM cell lines and primary patient myeloma cells. XmAb5592 also augmented antibody dependent cellular phagocytosis (ADCP) by macrophages. Natural killer (NK) cells became more activated by XmAb5592 than the IgG1 analog, evidenced by increased cell surface expression of granzyme B-dependent CD107a and MM cell lysis, even in the presence of bone marrow stromal cells. XmAb5592 potently inhibited tumor growth in mice bearing human MM xenografts via FcγR-dependent mechanisms, and was significantly more effective than the IgG1 analog. Lenalidomide synergistically enhanced in vitro ADCC against MM cells and in vivo tumor inhibition induced by XmAb5592. A single dose of 20 mg/kg XmAb5592 effectively depleted both blood and bone marrow plasma cells in cynomolgus monkeys. These results support clinical development of XmAb5592, both as a monotherapy and in combination with lenalidomide, to improve patient outcome of MM.     

Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu.

Treatment of advanced breast cancer with autologous stem cell transplantation is limited by a high probability of disease relapse. In clinical trials, interleukin 2 (IL-2) alone can expand natural killer (NK) cells in vivo and increase their cytotoxic activity against breast cancer cell lines, but this increase is modest. Understanding the mechanisms that mediate NK cell lysis of breast cancer targets may lead to improvements of current immunotherapy strategies. NK cells from normal donors or patients receiving subcutaneous IL-2 were tested in cytotoxicity assays against five breast cancer cell lines. The role of adhesion molecules and antibodies that interact through Fc receptors on NK cells was explored. NK cell lysis of breast cancer targets is variable and is partially dependent on recognition through ICAM-1 and CD18. While blocking CD2 slightly decreased cytotoxicity, contrary to expectations, an antibody against CD58 (the ligand for CD2), failed to block killing and instead mediated an increased cytotoxicity that correlated with target density of CD58. The CD58 antibody-enhanced killing was dependent not only on FcRgammaIII but also on CD2 and ICAM-1/CD18. To further elucidate the mechanism of this CD58 antibody-dependent cellular cytotoxicity (ADCC), another antibody was tested. Trastuzumab (Herceptin), a humanized antibody against HER2/neu, mediated potent ADCC against all the HER2/neu positive breast cancer targets. Unlike CD58 antibody-mediated ADCC, Herceptin ADCC was minimally affected by blocking antibodies to CD2 or ICAM-1/CD18, which suggests a different mechanism of action. This study shows that multiple mechanisms are involved in NK cell lysis of breast cancer targets, that none of the targets are inherently resistant to killing, and that two distinct mechanisms of ADCC can target immunotherapy to breast cancer cells.     

Subpopulations of human peripheral granulocyes and monocytes express receptors for IgA.

Receptors for the Fc portion of immunoglobin on human peripheral blood cells were enumerated by rosette formation with ox erythrocytes sensitized with rabbit IgG, IgA, and IgM. A large percentage of purified polymorphonuclear leukocytes and monocytes were found to express receptors for IgA. These receptors were also found to exist on a significantly greater percentage of lymphocytes than was previously observed. The receptors for IgA were specific, as verified by blocking studies using purified human immunogloblins. In addition, some polymorphonuclear leukocytes and monocytes were observed concomitantly to posses independent receptors for both IgG and IgA. These studies may indicate that IgA can cooperate with monocytes or polymorphonuclear leukocytes through receptors for IgA on these cells and perhaps mediate immune defense on mucosal surfaces. Initial studies on antibody-dependent cellular cytotoxicity suggested that IgA alone is ineffectual in supporting cytolysis by nonactivated human peripheral blood cells.     

IgA-mediated phagocytosis by mouse alveolar macrophages

Ingestion of antibody-opsonized sheep red blood cells by murine alveolar and peritoneal exudate macrophages was studied. Alveolar macrophages or peritoneal macrophages were isolated by lavage and incubated with TNP-SRBC, which had been preincubated with anti-DNP IgG, IgA, and IgE. Significant enhancement of phagocytosis by alveolar macrophages of TNP-SRBC was mediated by all classes of antibody examined, most markedly with IgG and less so with IgA and IgE. Enhancement of phagocytosis by peritoneal macrophages was mediated by IgG and IgE, but not by IgA. These results suggest that the interaction of IgA and Fc receptors for IgA on alveolar macrophages may increase the level of this cell's function in the mammalian lung to clear pathogens and immune complexes from the alveolar spaces.     

Surface markers of human eosinophils

Peripheral blood eosinophils from patients with eosinophilia and from healthy subjects were studied for surface immunoglobulins, receptors for the Fc region of IgG, complement receptors, and spontaneous rosette formation with sheep and mouse erythrocytes. Eosinophils were found to have receptors for complement and for aggregated IgG, and to have the same two types of complement receptors as do lymphocytes and monocytes. Immune adherence type receptors were specific for C4 or C3b, while C3d receptors were specific for C3d but unreactive with C4. Eosinophils differed from fully mature neutrophils in that the former had C3d receptors and relatively weak immune adherence (C4 or C3b) receptors, while the later did not have the C3d receptors and had strong immune adherence receptors. Eosinophil phagocytosis of complement-receptor bound erythrocytes was dependent on the presence of IgG in the antibody coating the red blood cells; this requirement for IgG resembled that found in neutrophil phagocytosis. No surface Ig or spontaneous erythrocyte rosette formation was observed with eosinophils.     

Characterization of effector cells in lymphocytotoxicity to autologous hepatocytes in HBsAg-positive and autoimmune chronic active hepatitis (CAH)

Peripheral blood lymphocyte subsets involved in cytotoxicity to autologous hepatocytes have been characterized by isolation on antibody-coated Petri dishes in autoimmune and HBsAg-positive chronic active hepatitis (CAH). In autoimmune CAH and in HBsAg-positive CAH without HBcAg in liver tissue, cytotoxicity is sustained by non-T lymphocytes and is confined to M1-positive cells bearing Fc receptors: M1 cytotoxicity inhibition by adding aggregated IgG suggests that these cells are responsible for an antibody-dependent cell-mediated mechanism (ADCC). Moreover, when T-enriched fractions were separated in T4, T8 and 5/9 positive subsets, only the first one showed a significant cytotoxicity: T4 positive cells might act as cytotoxic T cells or might be involved in delayed type hypersensitivity (DTH) reactions. Cytotoxic T lymphocytes in HBsAg-positive CAH with HBcAg in liver tissue are confined in T8 positive subset, while helper/inducer T cells (T4 positive or 5/9 positive) seem to play an important role only in the induction of cell-mediated injury against hepatocytes. The inhibition of T cell-cytotoxicity by preincubating liver cells with monoclonal antibody (Mab) anti-HLA AB and not with Mab anti-HLA DR or aggregated IgG supports the involvement of the class I major histocompatibility complex (MHC) expressed on the hepatocyte surface.     

Spontaneous and antibody-dependent cell-mediated cytotoxicity by human T cell subpopulations.

Human peripheral blood non-T cells, T cells and their subpopulations (Tmu, Tgamma, Tphi, Tgamma-depleted cells, and Tmu-depleted cells) were assayed for their capacity to mediated spontaneous lymphocyte-mediated cytotoxicity (SLMC) or natural killer activity against K562 tumor cell line and antibody-dependent cellular cytotoxicity (ADCC) against chicken erythrocytes coated with antibody. Non-T cells, unseparated T cells, Tgamma cells, and Tmu-depleted (Tgamma-enriched) cells were found to have both SLMC (NK activity) and ADCC. Tmu, Tphi, and Tgamma-depleted cells had minimal or no SLMC and ADCC activity. This study demonstrates that SLMC and ADCC activity in T cells is mediated by Tgamma cell subpopulations. These two cytotoxic reactions were either mediated by two distinct subsets of Tgamma cells or by a single effector cell using two different mechanisms.     

Monocyte-mediated antibody-dependent cell-mediated cytotoxicity: the role of the metabolic burst

Human monocytes respond to opsonized microorganisms with a "metabolic burst" composed of an increase in oxygen consumption, an increase in hexose monophosphate shunt (HMPS) activity, and the generation of reactive oxygen species (ROS). We investigated the role of the metabolic burst in antibody-dependent cell-mediated cytotoxicity (ADCC) by human monocytes toward anti-D coated erythrocyte target cells because recent studies suggested a role for oxygen-dependent bactericidal mechanisms in ADCC. In normal monocytes, we found that ADCC was nearly halved under hypoxic conditions. Several agents known to impair activation of the burst, such as vincristine, cation chelators, and a sulfhydryl reagent, all decreased cytotoxicity if added before initiation of contact between target and effector cells. Cytotoxicity was inhibited by 2-deoxyglucose but not fluoride, suggesting a nonglycolytic role for glucose in ADCC, perhaps in the HMPS pathway. Although these data suggested a role for the metabolic burst in ADCC, scavengers of ROS did not impair cytotoxicity, and monocytes from chronic granulomatous disease (CGD) patients who had a defective metabolic burst had normal levels of ADCC. We conclude that ADCC toward anti-D coated erythrocyte target cells was the result of at least two independent but closely related cytotoxic pathways. Although one of these pathways appeared to involve the metabolic burst, the potentially cytotoxic reactive oxygen species did not appear to play a role in this system.     

Cell Surface Heterogeneity of Human Blood Neutrophils and Monocytes

Until recently, human blood neutrophils (PMN) and monocytes have been considered to be homogeneous cell populations. However, much evidence has accumulated on their functional heterogeneity. This functional heterogeneity suggests the existence of different subsets of myeloid cells analogous to T and B subsets of lymphoid cells. The goal of this study was to investigate this question of myeloid subsets by examining myeloid cells for cell surface reactivity for IgG and complement (C). Normal PMN and monocytes were examined from 60 subjects for the presence of two types of IgG-Fc receptors and two activated C components, C3b and C3d. Most PMN and monocytes showed Fc receptor activity for rabbit IgG (Fc-R). In addition, the majority of monocytes but very few PMN reacted with human IgG (anti-Rh0) coated Rh-positive erythrocytes (Fc-H). Most PMN and monocytes showed C receptor reactivity for C3b, but only a minor subpopulation of both myeloid cells had C3d receptors. These data provide evidence that human blood myeloid cells may be composed of subsets with different membrane marker reactivities.