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R F Bargatze

Publications and source records attributed to R F Bargatze.

30 records · Page 2Linked to original sources
PubMed1987

Lymphoid tissue- and inflammation-specific endothelial cell differentiation defined by monoclonal antibodies.

Endothelial cells play an essential role in immune responses by regulating the entry of leukocytes into lymphoid tissues and sites of inflammation. As an initial approach to analyzing endothelial cell specialization in relation to such immune function, we have produced monoclonal antibodies (MAB) against mouse lymph node endothelium. Three antibodies were selected: MECA-20, recognizing the endothelium of all blood vessels in lymphoid as well as non-lymphoid organs; MECA-217, which stains the endothelium lining large elastic arteries, but among small vessels is specific for post-capillary venules within lymphoid organs and tissues exposed to exogenous antigen, such as skin and uterus; and MECA-325, an antibody that demonstrates specificity for the specialized high endothelial venules (HEV) that control lymphocyte homing into lymph nodes and Peyer's patches. MECA-325 failed to stain vessels in any non-lymphoid organs tested. Immunoperoxidase studies of HEV in lymph node frozen sections, and of isolated high endothelial cells in suspensions, demonstrated that the antigens recognized by all three antibodies are expressed at the cell surface; those defined by MECA-20 and MECA-325 are also present in the cytoplasm. To study the regulation of the antigens defined by these MAB in relation to extra-lymphoid immune reactions, we assessed their expression in induced s.c. granulomas as a model for chronic inflammation. Small vessels in the granulomas were already stained by MECA-217 in the first days of development. In contrast MECA-325 detected postcapillary venules (which frequently displayed the morphologic characteristics of HEV) only from approximately 1 wk, in parallel with the development of a persistent mononuclear cell infiltrate including numerous lymphocytes. The selective appearance of the MECA-325 antigen on vascular endothelium supporting lymphocyte traffic in both lymphoid and extra-lymphoid sites suggests that this antigen may play an important role in the process of lymphocyte extravasation. The demonstration of lymphoid organ- and inflammation-specific microvascular antigens offers direct evidence for a complex specialization of endothelium in relation to immune stimuli, and supports the concept that microvascular differentiation may play an important role in local immune responses.

Animals↗
PubMed1987

Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.

The tissue-specific homing of lymphocytes is directed by specialized high endothelial venules (HEV). At least three functionally independent lymphocyte/HEV recognition systems exist, controlling the extravasation of circulating lymphocytes into peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches or appendix), and the synovium of inflamed joints. We report here that antibodies capable of inhibiting human lymphocyte binding to one or more HEV types recognize a common 85-95-kD lymphocyte surface glycoprotein antigen, defined by the non-blocking monoclonal antibody, Hermes-1. We demonstrate that MEL-14, a monoclonal antibody against putative lymph node "homing receptors" in the mouse, functionally inhibits human lymphocyte binding to lymph node HEV but not to mucosal or synovial HEV, and cross-reacts with the 85-95-kD Hermes-1 antigen. Furthermore, we show that Hermes-3, a novel antibody produced by immunization with Hermes-1 antigen isolated from a mucosal HEV-specific cell line, selectively blocks lymphocyte binding to mucosal HEV. Such tissue specificity of inhibition suggests that MEL-14 and Hermes-3 block the function of specific lymphocyte recognition elements for lymph node and mucosal HEV, respectively. Recognition of synovial HEV also involves the 85-95-kD Hermes-1 antigen, in that a polyclonal antiserum produced against the isolated antigen blocks all three classes of lymphocyte-HEV interaction. From these studies, it is likely that the Hermes-1-defined 85-95-kD glycoprotein class either comprises a family of related but functionally independent receptors for HEV, or associates both physically and functionally with such receptors. The findings imply that related molecular mechanisms are involved in several functionally independent cell-cell recognition events that direct lymphocyte traffic.

Antibodies, Monoclonal↗
PubMed1987

Human lymphocyte and lymphoma homing receptors.

The migration of normal and malignant lymphocytes is controlled in part by selective lymphocyte recognition of high endothelial venules (HEV) at sites of lymphocyte exit from the blood. Recirculating lymphocytes appear to utilize structurally related, yet functionally distinct, 90-kD receptors to interact in an organ-specific manner with HEV in peripheral lymph nodes, in mucosa-associated lymphoid tissues (Peyer's patches, appendix), and in inflamed joint tissue (synovium). These lymphocyte "homing receptors" constitute a family of glycoprotein endothelial cell recognition elements that regulate the extravasation of circulating normal and neoplastic lymphocytes into different organs of the body, and thus play an important role in determining the characteristics of local immune responses and the patterns of dissemination of lymphoid neoplasms.

Animals↗
PubMed1986

A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man.

We describe a 90-kDa lymphocyte surface glycoprotein, recognized by the monoclonal antibody Hermes-1, that is involved in endothelial cell recognition and lymphocyte trafficking in man. This molecule is selectively expressed on normal or transformed lymphoid cells that are able to recognize and bind to high endothelial venules (HEV, specialized vessels that mediate lymphocyte exit from the blood into lymphoid organs); appears to be linked to HEV recognition function since, in fluorescence-activated cell sorting of variants of a cloned cell line, HEV binding ability co-selects with the Hermes-1 antigen; bears the predominant cell surface epitopes recognized by heterologous anti-human lymphocyte antibodies able to interfere with lymphocyte binding to HEV; and is structurally similar to a previously described mouse lymphocyte surface receptor for HEV. These findings demonstrate that the molecule defined by Hermes-1 either functions as a specific lymphocyte surface receptor for HEV, or is both precisely coregulated and physically and/or functionally associated with such receptors. The expression of this putative receptor for HEV on normal human lymphocyte populations parallels, and thus presumably helps determine, their migratory status in vivo. Hermes-1 should be a powerful tool for analyzing the role of endothelial cell recognition in the traffic of normal and neoplastic human lymphocytes.

Animals↗
PubMed1986

Homing receptors and the control of lymphocyte migration.

The traffic of lymphocytes is controlled in part by the selective interaction of circulating lymphocytes with specialized high endothelial venule (HEV) cells at sites of lymphocyte exit from the blood. At least three independent receptor systems are responsible for controlling lymphocyte traffic to different lymphoid organs or to sites of inflammation: one mediates lymphocyte interaction with HEV in peripheral lymph nodes, another in mucosa-associated lymphoid tissues, and a third in inflamed synovium. The receptors mediating lymphocyte recognition of HEV in different organs appear to be structurally related yet antigenically and functionally distinct 90 kD glycoproteins. Receptors for lymph node HEV can function as mammalian lectins, and probably interact with specific carbohydrate ligands on high endothelial cells. Mouse and human homing receptors share both antigenic and structural features, indicating a high conservation of lymphocyte-endothelial recognition systems during evolution. They play an essential part in the immune process by controlling lymphocyte traffic during B- and T-cell differentiation, and by segregating effector cells derived from stimulation in different tissues, thus simultaneously increasing the efficiency of organ-specific immune responses and decreasing possibilities for autoimmune crossreactions. Homing receptors are also expressed by many mouse and human lymphoid neoplasms, and appear to play a role in lymphoma metastasis. Related if not identical receptors are expressed by other leukocyte types, including polymorphonuclear leukocytes, monocytes, and large granular lymphocytes (natural killer cells). Thus lymphocyte homing receptors are members of a family of glycoprotein receptors for endothelium that control the extravasation of lymphocytes as well as other leukocytes, and help regulate both non-specific and specific immune responses in vivo.

Animals↗
PubMed1980

Induction of immunologic tolerance to the trimellitate haptenic group in mice: model for a therapeutic approach to trimellitic anhydride-induced hypersensitivity syndromes in humans?

IgE and IgG antibody responses to the trimellitate (TM) hapten group were elicited in mice by the intraperitoneal injection of the hapten coupled with keyhole limpet hemocyanin (KLH). Treatment of such previously sensitized mice with the same hapten coupled to synthetic copolymer of D-glutamic acid and D-lysine (D-GL) after primary immunization resulted in significant and specific suppression of anti-TM antibody responses in both IgE and IgG classes. These results provide direct evidence for the potential clinical usefulness of the D-GL immunotherapeutic approach to TMA sensitivity in humans.

Animals↗
PubMed1980

"Allergic breakthrough" after antigen sensitization: height of IgE synthesis is temporally related to diurnal variation in endogenous steroid production.

Mice of the SJL strain normally display the low IgE responder phenotype. In the course of extensive studies on IgE responses with this strain of mice, it because apparent that the magnitudes of IgE antibody synthesis by SJL mice varied after antigen sensitization either alone or in conjunction with exposure to optimal enhancing doses of whole body irradiation. Analysis of the basis for this variability revealed that SJL respond to antigen sensitization by displaying cyclical IgE response curves determined by the time of day the sensitization is carried out. Moreover, when these low responders are converted to the high responder phenotype by low dose irradiation, the time of irradiation determines the magnitude of the IgE response obtained, whereas the time of antigen challenge determines the potential for generating a good response. The diurnal curve of IgE responses in both unirradiated and irradiation-enhanced low responder mice appears to be determined by normal variations in levels of endogenous corticosteroids, as indicated by the correlation between the normal diurnal curve of endogenous steroid production with the cyclical pattern of IgE responses. This apparent effect of endogenous steroid production on IgE antibody synthesis is supported by experiments demonstrating that the normal IgE pattern in both unirradiated and irradiated mice can be perturbed by administration of cortisone at the proper time of day. These results indicate that IgE antibody synthesis displays unique sensitivity to fluctuations in plasma steroid levels and may have significant implications for the role of steroids in the pathogenesis and management of allergic diseases.

Adrenal Cortex Hormones↗
PubMed1979

Regulation of IgE antibody production by serum molecules. IV. Complete Freund's adjuvant induces both enhancing and suppressive activities detectable in the serum of low and high responder mice.

Two biologically active serum molecules manifesting precisely opposite biologic effects, both of which are selective for IgE antibody synthesis, can be detected in the serum and ascites fluids of CFA-immune mice. One activity, described previously, is suppressive and hence termed suppressive factor of allergy (SFA); the other, reported for the first time herein, is enhancing and has been termed enhancing factor of allergy (EFA). The ability to detect one vs the other activity requires certain special manipulations such as different doses of low dose x-irradiation. Conclusive evidence for the existence of two distinct factors mediating these two opposing biologic effects was obtained in studies demonstrating that affinity chromatography on concanavalin A-Sepharose segregated the two molecular entities. Thus, SFA binds poorly or not at all to Con A-Sepharose, whereas EFA binds to Con A and can be recovered in the eluate eluted with the competitive sugar alpha-methyl-D-glucopyranoside.

Animals↗
PubMed1979

Regulation of IgE antibody production by serum molecules. V. Evidence that coincidental sensitization and imbalance in the normal damping mechanism results in "allergic breakthrough".

Experiments presented in this paper were designed to test a new concept concerning the possible pathogenesis of the allergic phenotype. This concept, termed "allergic breakthrough" considers that one of the avenues toward the allergic phenotype involves coincidental sensitization combined with an imbalance in the normal damping mechanism that serves to limit IgE antibody production. The three predictions of this concept that can be tested experimentally are: 1) manipulations that are effective in heightening or re-establishing the damping mechanism should manifest persistence insofar as IgE antibody synthesis to the relevant allergen is concerned; 2) once allergic breakthrough has occurred, the height of production of IgE antibodies specific for the sensitizing agent should remain elevated at levels characteristic of the allergic phenotype, even after the threshold of damping activity has returned to a normal level; and 3) allergic breakthrough should display specificity in that breakthrough would occur in response to subsequent exposure to the specific antigen to which coincidental sensitization initially occurred, but not for other unrelated antigens. The studies presented herein confirm each one of these predictions, thereby providing substantial support for the validity of this concept as one possible distinguishing feature between individuals manifesting the nonallergic and allergic phenotypes, respectively.

Animals↗
PubMed1979

Immunologic tolerance to allergenic protein determinants: properties of tolerance induced in mice treated with conjugates of protein and a synthetic copolymer of D-glutamic acid and D-lysine (D-GL).

Conjugates of proteins and the synthetic copolymer of D-glutamic acid and D-lysine (protein-D-GL) reproducibly induce significant unresponsiveness to the protein antigens in experimental mice. Proteins studied include ovalbumin and antigen E of ragweed extract, the major allergen of ragweed pollen. The unresponsive state 1) can be induced in both unsensitized and previously sensitized experimental animals, 2) is selectively confined to responses of the IgE antibody class, 3) is long lasting, and 4) is highly antigen specific. IgE antibody responses can also be suppressed by administering comparable doses of unconjugated protein alone; however, the unresponsive state induced in this manner is only transient and rebound production of IgE antibody is often observed. Results from the studies of the cellular basis of the protein-D-GL induced unresponsiveness demonstrate that 1) protein-D-GL conjugates do not induce unresponsiveness at the level of protein-specific B cells, 2) tolerance is not induced by virtue of a detectable antigen-specific suppressor T cell mechanism, 3) tolerance is most probably induced in the antigen-specific helper T cell populations. The significant IgE-selective and antigen-specific tolerogenic activity of protein-D-GL conjugates make these compounds potential candidates for use as therapeutic agents in the treatment of IgE-mediated human allergic disorders induced by protein allergens.

Allergens↗