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Biomedical subjects

N Hogg

Publications and source records attributed to N Hogg.

At least 163 records · Page 9Linked to original sources
PubMed1988

The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immune response.

Monoclonal antibody RR 1/1 directed against the putative LFA-1 ligand molecule intracellular adhesion molecule-1 (ICAM-1) was found to inhibit the T cell proliferative response to the antigen PPD. Interestingly, the percentage of unstimulated monocytes which expressed ICAM-1 on their surface appeared to vary greatly from person to person although the majority of monocytes did express high levels of ICAM-1 within their cytoplasm and surface expression could be rapidly induced on most cells by adherence to fibronectin. Resting T cells showed no evidence of surface or cytoplasmic ICAM-1 although expression was induced both within the cell and on the membrane as a result of activation with phytohemagglutinin or a combination of OKT3 and phorbol 12,13-dibutyrate. The significance of these findings with respect to the function of monocyte and T cell in the generation of an immune response is discussed.

Adult↗
PubMed1988

Identification of a novel monocyte cell surface molecule involved in the generation of antigen-induced proliferative responses.

A monocyte molecule, identified by a monoclonal antibody (mAb) named 24, is involved in the antigen-specific proliferation of T cells. Several types of antigen-induced responses are blocked by mAb24, but mitogen responses, even at low doses, are not. The 24 molecule is found on circulating monocytes and no other cell type. Normally only a proportion of monocytes express the 24 molecule but it can be induced rapidly on monocytes in culture, possibly from intracellular sources. The epitope is present on a heterodimer of 175 and 95 kDa which is similar to the leukocyte cell adhesion molecule (Leu-CAM) family. These findings suggest that although the 24 molecule shows some functional and biochemical similarities with the Leu-CAM family of molecules, it represents a novel structure primarily associated with mononuclear phagocytes.

Antibodies, Monoclonal↗
PubMed1988

Neutrophil and monocyte cell surface p150,95 has iC3b-receptor (CR4) activity resembling CR3.

Previous investigations of p150,95 (CD11c), the third member of the CD18 membrane glycoprotein family that includes CR3 (Mac-1 or CD11b) and LFA-1 (CD11a), had demonstrated that solubilized p150,95 bound to iC3b-agarose in a manner similar to isolated CR3. The current study showed that membrane surface p150,95 also expressed iC3b-receptor activity and was probably the same as the neutrophil receptor for iC3b- or C3dg-coated erythrocytes (EC3bi or EC3dg) that had been previously designated CR4. Normal neutrophil and macrophage CR4-dependent EC3bi rosettes were inhibited by monoclonal anti-p150,95, and cells from a patient with CD18 deficiency did not form CR4-dependent EC3bi rosettes. With neutrophils that bore large amounts of CR1 and CR3 and little p150,95, EC3bi were found primarily via CR1 and CR3, and demonstration of p150,95-dependent rosettes required large amounts of fixed iC3b, low-ionic strength buffer, and antibody blockade of CR1 and CR3. By contrast, culture-derived macrophages expressed eight times more p150,95 than did monocytes and EC3bi were bound to both p150,95 and CR3 when EC3bi bore small amounts of fixed iC3b and assays were carried out in isotonic buffer. Comparison of the amounts of CR1, CR3, and CR4 in various tissues by immunoperoxidase staining revealed that CR4 was the most abundant C3 receptor molecule on tissue macrophages, and suggested that CR4 might be involved in clearance of C3-opsonized particles or immune complexes.

Animals↗
PubMed1988

Comparison of human monocytes isolated by elutriation and adherence suggests that heterogeneity may reflect a continuum of maturation/activation states.

Monocytes are heterogeneous both in terms of physical properties and in their functional capacity. Isolation of monocytes from peripheral blood may perturb the observed heterogeneity for purified cell preparations. To explore this possibility we examined monocytes prepared by two techniques, counter-flow centrifugation elutriation (CCE) and fibronectin adherence, in terms of cell-surface molecule expression and several physical properties. Although such cells would be expected to represent dissimilar cross-sections of the total monocyte population, they were found to have similar cell-surface antigenic profiles. Observed differences in levels of expression of several molecules (CR1, CR3 and the antigen recognized by LP9 antibody) were found to be a temperature-related phenomenon. These results indicate that monocytes are not divisible into 'subpopulations' on the basis of cell-surface molecule expression and suggest that heterogeneity of monocytes may reflect the presence in the circulation of a continuum of maturational/activation states.

Antibodies, Monoclonal↗
PubMed1987

Association of colorectal tumor epithelium expressing HLA-D/DR with CD8-positive T-cells and mononuclear phagocytes.

Forty-eight human colorectal adenocarcinomas, removed at different stages of development, have been examined immunohistochemically for the expression of class II molecules and for the relationship of such class II expression to infiltrating leukocytes. Forty-four% of tumor epithelium samples express class II molecules. This expression is confined to the proteins coded for by the HLA-D/DR subregion although the surrounding infiltrating cells express HLA-D/DR, -DQ, and -DP coded proteins. In addition, there are significantly greater numbers of mononuclear phagocytes and T-cells of the CD8 antibody-positive subset associated with the tumors expressing class II molecules on tumor epithelium compared to the class II-negative tumors. The T-cells appear not to be activated judging by the lack of expression of the receptor for interleukin-2 but the mononuclear phagocytes express CR1, the receptor for the complement component C3b, which suggests that they are stimulated.

Antibodies, Monoclonal↗
PubMed1987

Identification of IL 2R+ T cells and macrophages within rejecting rat cardiac allografts, and comparison of the effects of treatment with anti-IL 2R monoclonal antibody or cyclosporin.

Monoclonal antibodies to lymphokine-induced activation antigens of lymphocytes and macrophages were used to analyze the intragraft events occurring during acute rejection of rat heterotopic cardiac allografts. The cells present during untreated rejection were then compared with those present in situ after immunosuppression with the mouse anti-rat IL 2 receptor (anti-IL 2R) monoclonal antibody ART-18 or cyclosporin (CsA). Untreated rats rejected their grafts within 7 days, whereas rats receiving 10 days of i.v. ART-18 antibody therapy showed graft prolongation to more than 21 days, and rats receiving CsA for 7 days maintained their grafts indefinitely. Untreated rejection was associated with an influx of T (W3/13+) cells and macrophages (ED-1+, ED-2+). Activated mononuclear cells (IL 2R+) were identified within rejecting grafts from day 2, and their numbers peaked on days 4 to 6 when 15 to 20% of infiltrating leukocytes were IL 2R+. Double labeling studies of IL 2R+ cells present at day 6 showed surprisingly that both T cells and macrophages expressed IL 2R. In particular, although 55.8 +/- 6.9% (mean +/- SD) of IL 2R+ cells expressed the pan-T cell antigen 3/13, a similar proportion of IL 2R+ cells (49.8 +/- 8.2%) expressed the macrophage antigen ED-2. Conversely, both T cells and macrophage populations showed heterogeneity in their expression of IL 2R, because 39.2 +/- 12.2% of T cells and 31.0 +/- 13.4% of macrophages were IL 2R+. In addition, inflammatory macrophages at day 6 expressed the A1-3 antigen. Expression of this antigen by macrophages has previously been linked with development of macrophage procoagulant activity, and in this model intragraft inflammatory macrophages were closely associated with widespread deposits of fibrin. By comparison with untreated animals, rats treated with either ART-18 or CsA both lacked detectable IL 2R+ cells during the first 14 days post-transplantation (post-Tx), and showed significantly less cellular infiltration. However, although grafts of CsA-treated animals continued to remain IL 2R- and failed to stain with the macrophage activation marker A1-3, ART-18-treated rats showed increasing infiltration by both IL 2R+ mononuclear cells and A1-3+ macrophages, as well as increasing perivascular and interstitial fibrin deposition, prior to rejection by day 22. These studies document the presence of small number of activated intragraft T cells and macrophages during rat cardiac rejection, and show how CsA, and to a lesser extent anti-IL 2R therapy, inhibit this in situ activation and prolong graft survival. (ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Macrophage migration and maturation within rheumatoid nodules.

In long-established rheumatoid nodules, monocytes continue to be recruited and to migrate from the outer vascular zone toward the palisade and central necrotic area. Maturation of these cells is shown to take place during tissue migration. We found that the great majority of palisade cells express exclusive mononuclear phagocyte phenotypes. Among this mononuclear phagocyte population are many cells that bear the receptor for iC3b (CR3), but few that bear the receptor for C3b (CR1). HLA-D region molecule expression is intense and widespread.

Aged↗
PubMed1987

The role of monocyte lymphocyte function-associated antigen 1 (LFA-1) in accessory cell function.

Monoclonal antibodies directed against the common beta subunit shared by lymphocyte function-associated antigen-1 (LFA-1), CR3 and p150,95 or the alpha subunit of LFA-1, inhibited the T lymphocyte proliferative response to tetanus toxoid, pokeweed mitogen-1 and OKT3 but had little or no effect on the response to the leukoagglutinating lectins pokeweed mitogen-2 and phytohemagglutinin. The LFA-1 molecule was shown to participate in the adhesive interaction between monocytes and T lymphocytes that was required for the initiation of an immune response. Both monocyte and T lymphocyte LFA-1 were found to contribute to this interaction. These results further define the part played by the LFA-1 molecule in the activation of T lymphocytes.

Adult↗
PubMed1987

The human mononuclear phagocyte high-affinity Fc receptor, FcRI, defined by a monoclonal antibody, 10.1.

The properties of the mononuclear phagocyte (Mph) high-affinity Fc receptor, FcRI, were investigated using a novel monoclonal antibody (mAb) designated 10.1. This receptor was shown to be a protein of 71 kDa, presented chiefly on monocytes and the myeloid cell lines U937 and HL60. mAb 10.1 inhibited the binding to Mph of erythrocytes opsonized with rabbit IgG or human IgG3. It also blocked T cell proliferation induced by murine CD3 mAb of the IgG2a but not the IgG1 subclass. These results suggest that rabbit IgG, human IgG3 and murine IgG2a all bind to FcRI in a similar manner and that mAb 10.1 reacts with an epitope on FcRI near to the binding site for the Fc region of IgG. In addition, although it is well known that FcRI has a high affinity for both monomeric human IgG1 and IgG3, we show in this study that while erythrocytes opsonized with human IgG3 bind to Mph, equivalent cells opsonized with IgG1 surprisingly do not. These results define further the nature of the constraints on the interaction between Mph FcRI and particular IgGs.

Animals↗
PubMed1987

Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty tophi and rheumatoid nodules.

The mononuclear phagocyte infiltrate which occupies the gout tophus has been compared with that of the subcutaneous rheumatoid nodule. In the gout tophus, macrophage migration appears to be at a relatively low level and effectively terminates once these cells have been recruited into the corona. In the nodule the evidence suggests that both macrophage and granulocyte populations continuously migrate towards, and are progressively incorporated into, the necrotic centres. These observations indicate that chemotactic activity in rheumatoid nodules is at a higher level than in gout tophi, or that the rheumatoid mononuclear phagocyte is more responsive to such stimuli.

Aged↗
PubMed1987

Human immunodeficiency virus infection of monocytic and T-lymphocytic cells: receptor modulation and differentiation induced by phorbol ester.

The monocytic leukemic cell line U937 can be infected with human immunodeficiency virus type 1 (HIV-1) to become permanently infected virus producers. Uninfected U937 cells express T4 (CD4) antigen and form syncytia when mixed with HIV-1 producing cells. Anti-T4 monoclonal antibodies block syncytium formation indicating that the HIV-1 receptors on U937 cells include T4 antigen. The promyelocytic leukemic cell line HL60, while expressing only low amounts of surface T4 and not forming syncytia on exposure to HIV-1, can be infected by HIV-1 at lower efficiency than U937 and T-cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment induces the differentiation of U937 cells into macrophages. HIV-infected U937 cells retain the ability to differentiate, though less efficiently, as shown by the appearance of monocyte/macrophage surface markers. T4 antigen on both U937 and T-cell lines is down regulated by TPA treatment. Functional receptors for HIV-1, assayed by syncytium induction and pseudotype plating, are lost concomitantly with T4 antigen following TPA treatment of U937 cells and T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

A mononuclear phagocyte subset associated with cell necrosis in rheumatoid nodules: identification with monoclonal antibody 5.5.

A subset of mononuclear phagocytes identified by mAb 5.5 has been found within rheumatoid subcutaneous nodules. These cells appear to be derived directly from blood-borne monocytes. They form a variable proportion of the mononuclear phagocyte population within the nodule and are intimately associated with the tissue necrosis which characterizes these lesions. Necrosis appears within small aggregates of mAb 5.5-positive cells. Similar cells are also associated with localized extensions of necrosis through the palisade zone. Centrifugal extension of the necrotic centers through incorporation of the inner cells of the palisade layer appears to be an independent phenomenon.

Aged↗
PubMed1987

Tissue macrophage response in human papillomavirus infection and cervical intraepithelial neoplasia.

Tissue macrophages in the uterine cervix were studied immunocytochemically with monoclonal antibody (MoAb) 3.9 which reacts with the majority of macrophages, and E11 which is specific for the C3b receptor, CR1. Samples from five normal women, six with human papillomavirus (HPV) infection and 10 with cervical intraepithelial neoplasia (CIN) were tested. A small population of MoAb 3.9 positive and only occasional MoAb E11 positive macrophages were found in the normal cervix. In HPV infection and CIN there was a significant infiltration of MoAb 3.9 positive and MoAb E11 positive macrophages in both the epithelium and the stroma. The pattern of infiltration in these groups of women suggests that these macrophages were most likely to be functioning as the first line of defence against the spread of the virus infection, either through a direct anti-virus mechanism or non-specific phagocytosis.

Adult↗
PubMed1987

Elevation of infiltrating mononuclear phagocytes in human colorectal tumors.

The distribution of infiltrating monocytes-macrophages and T-lymphocytes in 45 primary colorectal tumors and 8 metastatic lymph nodes has been investigated by immunoperoxidase labeling with monoclonal antibodies (MoAbs). The number of lymphoreticular cells observed in tumor tissue, staged according to Dukes classification, was compared with paired normal tissue and between staged groups by statistical analysis. T-lymphocytes were not significantly elevated above the normal in either Dukes B or C stage tumors, although the IL-2 receptor (MoAb Tac) was expressed by varying numbers of T-cells in both groups. Mononuclear phagocytes increased numerically in both Dukes B (1.5-fold, P-value less than .01) and Dukes C tumors (2.5-fold, P-value less than .001) as compared to those in the uninvolved gut. In addition, the number of both total (MoAbs 3.9, 24) and stimulated mononuclear phagocytes expressing the C3b receptor (MoAb E11) was greater in metastasizing than in nonmetastasizing tumors (P-value less than .01). Thus the T-cell-to-monocyte ratio was altered from 2:1 in normal tissue to 1:1 in advanced tumors. The stromal environment around tumor cells in lymph nodes was similar to that of the primary tumor, but there was a reduction in the proportion of cells expressing the C3b receptor; unlike the primary tumor, there was virtually no infiltration of the tumor epithelium. Although there is a significant alteration in the mononuclear phagocyte population within colorectal tumors, there is no histologic evidence for a cytotoxic role for these cells.

Antibodies, Monoclonal↗
PubMed1986

Imaging thrombus with radiolabelled monoclonal antibody to platelets.

Indium-111-hydroxyquinoline labelled platelets, though useful in the detection of thrombus, have not gained widespread use owing to the time and technical skill required for their preparation. A study was therefore conducted evaluating a new method of imaging thrombus with platelets radiolabelled with a 111In labelled monoclonal antibody, P256, directed to the platelet surface glycoprotein complex IIb/IIIa. When the number of receptors occupied by P256 was less than 3% of the total available on the platelet surface platelet function, as assessed by platelet aggregometry, was undisturbed. P256 was radiolabelled with 111In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo--that is, by direct intravenous injection of P256--in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The 111In kinetics recorded after intravenous P256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P256, three had documented thrombus, two of whom gave positive results on P256 platelet scintigraphy. The third subject had chronic deep venous thrombosis and was scintigraphically negative. Imaging thrombus using a radiolabelled monoclonal antibody directed to platelets appears to offer great potential as a simple, non-invasive approach to the diagnosis of thrombosis.

Animals↗