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M M Kay

Publications and source records attributed to M M Kay.

At least 73 records · Page 4Linked to original sources
PubMed1983

Polypeptides immunologically related to band 3 are present in nucleated somatic cells.

Band 3, the major transmembrane polypeptide of erythrocytes, mediates the exchange of anions (chloride and bicarbonate) across the membrane. We suspected that band 3 was present on nucleated somatic cells as well as erythrocytes because the senescent cell antigen that is immunologically related to band 3 is present on lymphocytes, platelets, adult liver cells, and embryonic kidney cells; and antibodies prepared against the senescent cell antigen isolated from leukocytes react with erythrocyte band 3. For this reason, we examined human fibroblasts, lung cells, neutrophils, mononuclear leukocytes, squamous epithelial (mouth) cells, lung squamous epithelial carcinoma, mouse neuroblastoma cells, and rat hepatocytes for immunoreactive forms of band 3 by using monospecific antibodies to erythrocyte band 3. The results demonstrated that polypeptides sharing common antigenic determinants with erythrocyte band 3 are present in nucleated somatic cells as determined by immunofluorescence, immunoelectron microscopy, and immunoautoradiography. Peptide mapping revealed substantial sequence homology between erythrocyte band 3 and the band 3-like protein of leukocytes. Immunofluorescence studies indicate that the band 3-like proteins in nucleated cells participate in antibody-induced cell surface capping.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1983

Senescent cell antigen is immunologically related to band 3.

IgG autoantibodies in human serum selectively bind to a glycopeptide antigen that appears on senescent and damaged cells in situ. We identified the membrane protein from which the senescent cell antigen is derived by using a phagocytosis-inhibition assay and immunoautoradiographic gel staining and electroblotting techniques. Results of the phagocytosis-inhibition assay revealed that only the purified transmembrane glycoprotein designated "band 3" and senescent cell antigen inhibited the phagocytosis of erythrocytes induced by IgG eluted from senescent erythrocytes. Purified spectrin, syndein, band 4.1, actin, glycophorin A, and intact or desialylated sialoglycoprotein periodic acid/Schiff (PAS) staining bands 1-4 containing glycophorins A, B, and C did not inhibit phagocytosis. Specific antibodies against the senescent cell antigen and erythrocyte band 3 were used to identify the membrane protein from which the senescent cell antigen is derived. Band 3-related polypeptides (MrS approximately equal to 60,000, 42,000, and 18-26,000) were identified in erythrocyte ghosts prepared in the presence of diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride, and EDTA by immunoautoradiography with antiband 3. Antibodies to senescent cell antigen reacted with band 3 and the same lower Mr band 3-related polypeptides. Thus, the senescent cell antigen is immunologically related to band 3.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1982

Antigenicity, storage, and aging: physiologic autoantibodies to cell membrane and serum proteins and the senescent cell antigen.

Normal human serum contains autoantibodies to a wide range of cellular and serum proteins. IgG autoantibodies to cell membrane proteins spectrin, syndein (Band 2.1), Band 3 degradation products, and the senescent cell antigen are among them. Physiologic autoantibodies to the senescent cell antigen, a approximately 62 000 dalton glycopeptide derived from Band 3, initiate removal of senescent, damaged, and stored cells in vivo. The senescent cell antigen is one of the two Band 3 degradation products (Mr approximately 66 000 and 62 000) observed in freshly prepared ghosts. Since the senescent cell antigen is observed on red cells aged in situ, data suggest that Band 3 undergoes proteolysis in situ. IgG eluted from blood stored for transfusion binds to the senescent cell antigen. The amount of IgG on red cells increases during storage suggesting accumulation of the senescent cell antigen. Autoantibodies to other cell and serum proteins are discussed as possible regulators of homeostasis. The effect of age on physiologic autoantibodies is reviewed.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1981

Isolation of the phagocytosis-inducing IgG-binding antigen on senescent somatic cells.

To remove senescent red blood cells (RBCs) from the circulation, macrophages must distinguish them from mature RBCs. That is achieved by a specific recognition system. An antigen that develops on the surface of a senescing RBC is recognized and bound by the Fab region of an IgG autoantibody in the serum. Subsequently the Fc region of the autoantibody is recognized and bound by a macrophage, which proceeds to phagocytose the RBC. The antigenic molecule can be extracted from senescent but not young RBCs with Triton X-100 (ref. 4), although 10--30% as much antigen can be extracted from middle-aged as from senescent RBCs. I have now used IgG autoantibodies eluted from senescent RBCs to isolate and purify the IgG-binding antigen on senescent RBCs, and to detect the antigen on other somatic cells. The antigen is a congruent to 62,000-Mr protein which is present on stored platelets, lymphocytes and neutrophils, and on cultured human adult liver and embryonic kidney cells, as well as senescent RBCs.

Antigens, Surface↗
PubMed1981

An age-specific cell antigen is present on senescent human red blood cell membranes. A brief note.

Immunoglobulin G autoantibodies selectively bind to senescent human red blood cells (RBC) in situ and initiate their removal by phagocytosis. In this paper, we characterize the IgG binding receptor appearing on senescent RBC using glycophorin-enriched vesicles prepared by Triton X-100 extraction of young, middle-aged, and old RBC populations. These vesicles contain all known sialoglycoproteins and trace contaminants of other proteins. IgG binds predominantly to vesicles from old cells, as determined by both 125I-labeled protein A binding to IgG molecules and an erythrophagocytosis-inhibition assay. Addition of lipids does not alter IgG binding. Liposomes prepared from lipids of young and old cell fractions do not bind significant amounts of IgG. IgG binding is reduced following trypsin treatment of vesicles. The data suggest that the age-specific cell antigen is a protein which co-purifies with sialoglycoproteins, but is not identical with glycophorin. Since it is extracted predominantly from senescent cells, a chemical modification within the membrane may either form the age-specific cell antigen during aging or render it accessible during senescence.

Antigens↗
PubMed1981

The IgG autoantibody binding determinant appearing on senescent membranes residues on a 62000 MW peptide.

Mechanisms by which macrophages recognize and remove senescent red blood cells (RBC) were investigated. Present evidence indicates that the antigen binding portion of immunoglobulin G (IgG) autoantibodies in normal serum selectively binds to senescent RBC in situ and initiates their removal by mononuclear phagocytes. IgG autoantibodies eluted from senescent RBC were conjugated to cyanogen bromide activated Sepharose 4B, and used to isolate and purify the IgG binding receptor. Sialoglycoprotein mixtures were processed with the senescent cell IgG affinity column. Gel electrophoresis of the bound material eluted from the column revealed a single band migrating with a molecular weight of approximately equal to 62000. This isolated peptide, but not the sialoglycoprotein mixture from which it was isolated, absorbed the phagocytosis inducing ability of IgG. Thus, the senescent cell antigen to which IgG binds, is a 62000 Dalton glycopeptide.

Autoantibodies↗
PubMed1981

Homeostatic removal of senescent murine erythrocytes by splenic macrophages.

Removal of senescent erythrocytes (RBC) from the circulation was investigated both in vivo and in vitro using inbred BALB/C mice as a model. Murine RBC were pulse-labeled in situ with 59Fe, and young and old peripheral blood RBC were separated by density gradient centrifugation on Percoll gradients. 59Fe labeled young RBC were found at a density of p 1.09. Forty days after 59Fe pulse labeling, 59Fe labeled RBC were found at p = 1.11 and 1.12, 59Fe labeled young or old cells were transfused into mice. Peripheral blood and spleen cell populations (i.e., macrophages, lymphocytes, polymorphonuclear leukocytes, and RBC) were assessed for radioactivity at varying time intervals after young or old RBC injection. Spleen cell populations were separated by density gradient centrifugation. The results revealed that senescent RBC were cleared more rapidly from the peripheral blood than were young RBC. and that the rate was related to the incorporation of senescent RBC by splenic macrophages. Studies performed in vitro revealed that splenic macrophages phagocytized autologous senescent RBC but not autologous young RBC. Thus, splenic macrophages can function as homeostatic regulators by selectively phagocytizing senescent cells in situ. Development of a murine model for RBC clearance studies should facilitate further studies on mechanisms of macrophage recognition of effete self RBC and other somatic cells.

Animals↗
PubMed1979

Age-related changes in the immune system of mice of eight medium and long-lived strains and hybrids. I. Organ, cellular, and activity changes.

Fifty-three organ, cellular and activity indices were assessed in aging mice of 8 strains and hybrids (5 inbred strains, 1 random bred strain and 2 hybrids of inbred strains) in an attempt to determine which aspects of immunologic aging are characteristic of the species. The results indicate that thymic weight, cellular, and activity indices exhibit a statistically significant negative correlation with age for mice of all 8 strains and hybrids; and B cell cellular indices show a statistically significant positive correlation with age for all mice, while the B cell activity index, lipopolysaccharide response, is dependent on the strain or hybrid. This correlation study supports the view that the T cell component of the immune system deteriorates with age while the B cell component remains relatively intact. Further, the results suggest that thymic aging is a characteristic of the mouse species and that the intrinsic "clock" for immunologic aging resides in the thymus, because most splenic and lymph node T cell activity and cellular indices are associated with thymic weight and cellular indices. Finally, the findings that indices which correlate best with age show the same trend for all strains and hybrids examined suggest that (a) if randomly occurring somatic mutation does play a role in immunologic aging, its influence is limited, and (b) genetic factors not easily influenced by environmental factors regulate immunologic aging.

Aging↗
PubMed1979

Age-related changes in the immune system of mice of eight medium and long-lived strains and hybrids. II. Short- and long-term effects of natural infection with parainfluenza type 1 virus (Sendai).

Studies on the effects of natural infection with parainfluenza type 1 virus (Sendai) on the immune system of 8 strains and hybrids of aging mice revealed that (a) 55 of 63 indices tested were abnormal as late as 8 months after the disappearance of clinical systoms, (b) thymus weight and cell indices and lymph node T cell activity still exhibited a statistically significant negative correlation with age following infection, and (c) immunologically immature young and immunodeficient old mice suffered more severe sequelae following viral infection than did adult or middle-aged mice as determined by accelerated decline of thymus indices, mortality, IgM Coombs' titer, and in the case of old mice, anemia. These findings suggest that chronic viral infection can accelerate immunologic aging and that viral infection in utero can suppress or retard the development of the T cell component of the immune system. In support of our previous study, they also suggest that the thymus regulates immunologic aging and that genetic factors regulating immunologic aging are not easily influenced by environmental factors.

Aging↗
PubMed1979

An overview of immune aging.

A brief overview of the effect of age on the function of cells of the immune system is presented. Normal immune functions can begin to decline shortly after an individual reaches sexual maturity. Foremost among the cellular changes are those in the stem cells as reflected in their growth properties and the availability of precursor T cells, and in the T cell where a shift in subpopulations may be occurring. Present evidence indicates that thymic involution precedes and therefore may be responsible for the age dependent decline in the ability of the immune system to generate functional T cells. It now appears that the primary effect of thymic involution is on a T cell differentiation pathway affecting the more mature T cells first and only later the less mature T cells. Thus, the thymus may be the aging clock for the immune system. Future studies should be centered around processes regulating growth and atrophy of the thymus.

Aging↗
PubMed1978

Role of physiologic autoantibody in the removal of senescent human red cells.

The mechanism by which mononuclear phagocytes distinguish mature "self" from senescent "self" was investigated. Evidence is presented indicating that human mononuclear phagocytes distinguish senescent RBC from mature RBC on the basis of selective Ig attachment to the membranes of senescent cells. This Ig, eluted from senescent human RBC, was shown to be IgG and free of other Igs by immunodiffusion, immunoelectrophoresis, and polyacrylamide gel electrophoresis. The IgG was polyclonal with respect to light chains. The eluted IgG reattaches to homologous stored RBC, but not to mature autologous or allogeneic RBC, via the Fab region. It then initiates phagocytosis of these stored RBC by mononuclear phagocytes. Evidence suggests that the IgG is directed against altered membrane receptors. Thus, this IgG may be a "physiologic" autoantibody and contribute to the maintenance of homeostasis by performing regulatory function.

Adult↗