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Biomedical subjects

C Hammerberg

Publications and source records attributed to C Hammerberg.

At least 55 records · Page 3Linked to original sources
PubMed1990

IL-1 activity is reduced in psoriatic skin. Decreased IL-1 alpha and increased nonfunctional IL-1 beta.

IL-1 may influence or be influenced by a number of abnormalities present in psoriasis; including keratinocyte proliferation, eicosanoid production, fibroblast activation, endothelial cell adhesiveness, T cell infiltration and activation, cyclic nucleotide metabolism, and transmembrane signal transduction mechanisms. We assessed IL-1 regulation in normal, uninvolved, and involved skin of psoriatic patients using immunofluorescence microscopy, a sensitive ELISA method to quantitate immunoreactive IL-1 beta and IL-1 alpha protein levels, the thymocyte proliferation costimulation assay, costimulation of the LBRM.33 IL-1-sensitive cell line, and Northern blotting of cellular RNA to quantitate IL-1 alpha and beta mRNA. IL-1 beta was easily detectable by immunofluorescence microscopy and found to be localized predominantly in epidermal keratinocytes, whereas IL-1 alpha was not detectable with this method. Immunoreactive IL-1 beta was found to be elevated in cytosolic extracts derived from involved psoriatic keratomes relative to keratomes of normal skin. The elevated IL-1 beta protein was accompanied by elevated levels of IL-1 beta mRNA in psoriatic skin relative to normal skin. In contrast, immunoreactive IL-1 alpha levels were markedly reduced in lesional psoriatic skin. In functional assays using both the thymocyte proliferation assay and the LBRM.33 cell line, IL-1 activity from psoriatic involved skin keratomes was markedly reduced relative to that of uninvolved psoriatic keratomes and normal skin. All activity of both normal and psoriatic skin was attributable to IL-1 alpha. The elevated IL-1 beta immunoreactive protein present in psoriatic skin was found to be functionally inactive in these assays. The inactivity of the IL-1 beta was not due to an artifact of the cytosolic method of preparation because IL-1 beta released by psoriatic skin into the media was also nonfunctional. This was in keeping with the demonstration that the IL-1 beta was nonfunctional despite existing as a processed molecule. Taken together, these data demonstrate uncoordinated regulation of IL-1 alpha and Il-1 beta in psoriasis. The profound and complex changes in this system suggest IL-1 dysregulation may be integrally involved in the inflammatory, biochemical, and proliferative processes involved in the pathophysiology of psoriasis.

Biological Assay↗
PubMed1990

Cicatricial pemphigoid. Identification of two distinct sets of epidermal antigens by IgA and IgG class circulating autoantibodies.

A patient with severe cicatricial pemphigoid demonstrated both in vivo bound and circulating anti-basement membrane zone antibodies of the IgA and IgG classes. Complement component 3 (C3) was also deposited in the basement membrane zone of lesional skin as well as in normal-appearing buccal mucosa of the patient. However, C1q was absent, while granular deposits of two factors of the alternative complement activating pathway, properdin and properdin factor B, were present only in the basement membrane zone of lesional skin, but not in normal buccal mucosa. Deposition of alternative complement pathway reactants in the lesion suggests that complement activation by IgA was associated with lesion development. Western blot analysis of the patient's serum on electrophoresed cultured keratinocyte antigens identified two distinct sets of epidermal antigens. While IgG bound antigens of 230, 205, 140, and 90 kd, the patient's IgA antibodies bound a distinct set of antigens, 180 and 130 kd. The potential pathogenic role of IgA in cicatricial pemphigoid is discussed.

Aged↗
PubMed1990

UM4D4+ (CDw60) T cells are compartmentalized into psoriatic skin and release lymphokines that induce a keratinocyte phenotype expressed in psoriatic lesions.

UM4D4 (CDw60), the surface molecule of a novel antigen-independent T-cell activation pathway, was found to be highly expressed on lesional psoriatic T cells. To examine whether UM4D4 represents a T-cell activation pathway for psoriatic T cells, a T-cell line was initiated from an acute skin lesion and cloned by limiting dilution. Clonality was verified by analysis of T-cell receptor gene rearrangement. All T-cell clones tested, whether CD4+2H4+CD8-, CD4+2H4-CD8-, or CD4-CD8+CD11b-, expressed UM4D4 and were activated by the monoclonal antibody anti-UM4D4. Lesional psoriatic T-cell clones were heterogeneous in the degree of anti-UM4D4-induced proliferation and in their production of IL-2 and gamma-interferon. Lymphokines released by anti-UM4D4 activation were capable of inducing ICAM-1 and HLA-DR expression on cultured normal keratinocytes. Thus, the high expression of UM4D4 on T-cells in psoriatic skin provides an alternative mechanism for T-cell activation that may be operative in the psoriatic lesional milieu. Indeed, activation of lesional T-cells through the UM4D4 molecule resulted in release of lymphokines that directly induced keratinocytes to express a phenotype displayed in psoriatic skin lesions.

Antigens, CD↗
PubMed1990

Interleukin-1 in human skin: dysregulation in psoriasis.

Cytokine dysregulation is an attractive concept to explain many of the observed abnormalities in psoriasis. IL-1, in particular, can potentiate immune cellular activation, activate fibroblasts, and increase endothelial cell adhesiveness to leukocytes. Here, we review IL-1 regulation in normal and psoriatic skin in vivo in relation to normal skin and cultured keratinocytes. Contrary to expectations, IL-1 functional activity in psoriatic lesions is reduced, not increased, relative to normal skin. The reduction is attributable to the presence of IL-1 inhibitors, reduced IL-1alpha levels, and an IL-1beta that lacked function in T-cell assays. IL-1beta protein is actually significantly increased in psoriatic lesions, but the mechanism of its non-functionality remains unclear. Unlike cultured keratinocytes, which accumulate large, inactive IL-1beta precursors, both normal and psoriatic skin process IL-1beta to a mature form. Novel mechanisms of post-translational processing by epidermis in vivo may generate a novel form of IL-1beta with unknown functions. The marked abnormalities of IL-1 regulation in psoriatic skin suggest that this molecule may be important in normal skin homeostasis.

Humans↗
PubMed1990

Humoral and cell-mediated immune response and performance of weaned pigs fed four supplemental vitamin E levels and housed at two nursery temperatures.

Three trials using 80 Yorkshire x Hampshire x Duroc crossbred pigs (avg initial wt, 6.9 kg) were conducted to determine the effects of four dietary vitamin E levels (11, 110, 220 and 550 IU/kg of feed) on the humoral and cell-mediated immune response and performance of 4-wk-old weanling pigs housed at two nursery temperatures (19 or 30 degrees C). Interactive effects of temperature and vitamin E were not observed for any measurements. Serum and liver vitamin E levels increased linearly with increasing level of dietary vitamin E, but performance, cortisol, antibody levels and mitogen-induced stimulation indices were not affected by supplemental levels of vitamin E. Average daily gain and feed intake were higher (P less than .01) for pigs housed at 19 degrees C than for pigs housed at 30 degrees C, but feed:gain ratios, mitogen stimulation index of white blood cells, plasma cortisol levels and antibody titers were not altered. Although supplemental vitamin E above the NRC estimated requirement increased serum and liver vitamin E concentrations, no differences were observed in humoral and cell-mediated immune response, cortisol levels or performance for weanling pigs housed at either 19 or 30 degrees C temperatures.

Animals↗
PubMed1989

Immunodeficiency in young pigs.

Immunodeficiency in neonatal and young pigs was studied in terms of T-cell function. Generalized T-cell deficiency did not exist in young pigs on the basis of the in vitro response of blood mononuclear cells to a polyclonal T-cell mitogen, phytohemagglutinin. However, immunodeficiency that extended from birth up to 4 weeks, was observed in serum antibody concentration and in vitro proliferative responses of blood mononuclear cells from young pigs exposed to a low antigen dose of a T-cell dependent antigen, egg white lysozyme. The low in vitro proliferative response to lysozyme was not attributable simply to a lack of interleukin-2 production, because supplementation with human interleukin-2 did not enhance the in vitro cellular response. Also, pokeweed mitogen-stimulated B cells from young pigs up to the age of 5 to 6 weeks produced immunoglobulin concentration, which also was not affected by the addition of human interleukin-2 to the in vitro cultures. The blood mononuclear cells obtained from pigs within the first 5 to 6 weeks after birth and incubated with monoclonal antibodies reactive to all T cells (MSA4), helper T cells (74-12-4) or suppressor/cytotoxic T cells (76-2-11) did not yield consistent excess of suppressor/cytotoxic T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Isolation of an antigenically "null" cell line from pig peripheral blood mononuclear cells.

A new pig cell line (A4) isolated from a primary culture of pig peripheral blood mononuclear cells was characterized. A4 was demonstrated to be morphologically, antigenically and functionally distinct from the more commonly isolated pig lymphoblastoid B cell lines (e.g. P-SC). When the A4 cell line and clones derived from it were tested against a panel of monoclonal antibodies, which define specific subpopulations of pig mononuclear cells, little or no reactivity was observed. The A4 cell line, unlike the P-SC cell line, was unable to induce a mixed lymphocyte reaction. The amount of immunoglobulin secreted by A4 cells as detected by an ELISA was reduced compared to that produced by P-SC cells. The P-SC cell lines produced an IL-1-like factor, whereas no IL-1-like activity was found in the A4 supernatant. The A4 cell line appeared to be a null cell in respect to the P-SC cell line properties; only the slight amount of immunoglobulin produced suggested that the A4 cell line is of the B cell lineage. An association of viral particles with cells of the A4 morphology and null antigenic characteristics was observed and may provide an explanation for the reduced B cell properties of A4 cells.

Animals↗
PubMed1988

Taenia taeniaeformis: cellular reconstruction of athymic mice and role of L3T4+ helper T lymphocytes in the early infection.

The role of T helper lymphocytes (L3T4+) in the early response to Taenia taeniaeformis metacestodes was investigated. Athymic BALB/c-nu/nu mice (susceptible) were inoculated intraperitoneally with the following cell populations from congenic BALB/c-nu+ + mice (resistant): (a) whole spleen single cells, (b) thymus single cell suspensions, or (c) spleen cells pretreated with anti-L3T4 monoclonal antibody before the injection. The mice were given 3 weekly injections of cells and then infected orally with 300 eggs 7 days after the last injection. Cryostat sections of the liver from the infected mice were examined at 6 days postinfection (PI) for parasite viability, the numbers of eosinophils, and L3T4+ T lymphocytes present within 100 micron of the parasite and for the presence of biotin in hepatocytes (involved in biosynthesis of fatty acids) around the parasite. The success of the cellular reconstitution of athymic mice with the lymphoid cells was measured by a T-cell mitogenic assay with concanavalin A (ConA). The cellular reconstitution of athymic mice with a mixture of lymphoid cells from the spleen and thymus of BALB/c-nu/ + mice resulted in both parasite death and eosinophil infiltration. Reconstitution with mature splenic cells alone resulted in a greater parasite killing and eosinophil infiltration as compared to reconstitution with thymic cells. The better reconstitution with splenic cells was reflected in a greater mitogenic response to ConA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Evaluation of spleen lymphocyte responsiveness to a T-cell mitogen during early infection with larval Taenia taeniaeformis.

The effect of taeniid infection on the in vitro cellular response of the host was investigated. Infections of Taenia taeniaeformis decreased the ability of spleen cells from susceptible C3H/He mice to respond to the T-cell mitogen concanavalin A (Con A) as early as 2 days postinfection (pi) reaching a suppression peak at day 12 pi. Similar experiments performed with spleen cells from infected BALB/c mice, resistant to the infection, revealed little or no suppression of Con A stimulation. The results suggested that susceptibility to the parasite may be due to its ability to induce a partial suppression of the host's immune system. The role of adherent splenocytes from infected C3H/He mice in the production of a deficient response to Con A during early infection was studied by coculturing experiments. These experiments demonstrated that adherent populations from infected mice did not play a direct role in the Con A-suppressor mechanisms. Concomitant with the suppressor activity an increased background proliferation was observed with nonstimulated splenocytes from C3H/He mice infected with T. taeniaeformis. Plasma from infected mice was able to suppress the response of normal spleen cells to Con A and to stimulate a proliferative response in cultured splenocytes from noninfected animals. The results suggest the presence of factors in the plasma of infected mice which may be modulating the immune response to the parasite.

Animals↗
PubMed1987

Taenia taeniaeformis: early inflammatory response around developing metacestodes in the liver of resistant and susceptible mice II. Histochemistry and cytochemistry.

Female BALB/cJ (resistant), C3H/HeJ (intermediate resistant), and C3H/HeDub (susceptible) inbred mice, 4-5 wk old, were infected with Taenia taeniaeformis. Liver sections were stained for the enzymes acid phosphatase, beta-glucuronidase, and peroxidase. Eosinophils present around the parasite were identified by the ethanolic Congo red method. Possible gross changes in lipid metabolism in the hepatocytes surrounding the parasite were investigated with the Sudan black B method. The results of observations made by light microscopy were: (1) beta-glucuronidase activity above background levels was observed only in the hepatocytes around the parasite in BALB/cJ mice at 4, 5, and 6 days postinfection (PI); no reaction was observed in the other 2 strains of mice studied; (2) acid phosphatase activity was very strong at 2, 3, and 4 in the 3 strains of mice while this reactivity was weak at 5 and 6 days PI; (3) the cytoplasm of the hepatocytes around the metacestode stained more heavily with Sudan black B than other hepatocytes; and (4) the presence of eosinophils appearing at 3 days PI around the parasite in all 3 strains of mice was demonstrated by staining with Sudan black B, the substrate of peroxidase, and Congo red. Infected C3H/HeJ and BALB/cJ mice had higher numbers of liver eosinophils than infected C3H/HeDub mice throughout the observation time. The present results suggest 2 conclusions: (1) a parasite-liver interaction occurs as is evident by hepatocyte changes in beta-glucuronidase activity and Sudan black B staining, and (2) resistance to the early stages of T. taeniaeformis is associated with the appearance of eosinophils.

Acid Phosphatase↗
PubMed1987

Taenia taeniaeformis: early inflammatory response around developing metacestodes in the liver of resistant and susceptible mice I. Identification of leukocyte response with monoclonal antibodies.

Female BALB/cJ (resistant), C3H/HeJ (intermediate resistant), and C3H/HeDub (susceptible) inbred mice, 4-5 wk old, were infected with Taenia taeniaeformis. Liver sections were stained by an immunoperoxidase technique (avidin-biotin complex, ABC) for the differentiation antigens Lyt-1, Lyt-2, Mac-1, Mac-2, Mac-3, and B220. Binding of ABC to the cytoplasm of hepatocytes around the developing parasite was observed at 4 days postinfection (PI) in all 3 strains of mice, persisting in BALB/cJ and C3H/HeJ liver sections at 5 and 6 days PI, suggesting the presence of high concentrations of biotin, a fatty acid synthesis mediator. Two cell populations were labeled with B220 monoclonal antibodies: lymphocytes and polymorphonuclear (PMN) cells. At 4 days PI the number of labeled PMN cells peaked in infected C3H/HeJ and BALB/cJ mice; however a low number of PMN cells were labeled in infected C3H/HeDub mice. Few lymphocytes bound the B220 antibody in either BALB/cJ, C3H/HeJ, or C3H/HeDub infected mice. The number of Mac-1+ cells detected in infected C3H/HeJ and BALB/cJ liver sections were similar whereas fewer Mac-1+ cells were present in infected C3H/HeDub mice. Mac-2+ cells appeared in high numbers around the growing parasite at 5 and 6 days PI in the liver of C3H/HeDub mice, but not in the liver of BALB/cJ mice. Mac-3+ cells followed a similar pattern to that of the cell population defined by Mac-2. Few Lyt-1+ and Lyt-2+ cells were detected around the parasite site in the 3 strains of mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Characterization of monoclonal antibodies directed against swine leukocytes.

Hybridomas were produced from fusions of the SP2/0 mouse myeloma with splenic cells from: 1) an outbred Sprague Dawley rat immunized with swine peripheral blood mononuclear (PBM) cells; 2) a (CBA/NDub X BALB/c Dub) F1 mouse immunized with concanavalin A (Con A) activated swine PBM cells and 3) a (BALB/c Dub X C3H/He Dub) F1 mouse immunized with swine thymocytes. The resulting supernatants were screened by a microcytotoxicity assay for activity against swine PBM cells. Four hybridomas (MSA1, MSA2, MSA3 and MSA4) were selected, cloned and characterized by their cell reactivity and effect on mitogenic assays. MSA1 and MSA2 belong to the rat IgG2b subclass. MSA3 and MSA4 are of the mouse IgG2a subclass. These monoclonal antibodies reacted in the following manner: MSA1 with monocytes, granulocytes, red blood cells and bone marrow cells; MSA2 with subset of T cells; MSA3 with B cells and subsets of T cells and monocytes (class II molecule) and MSA4, a pan-T cell reagent (E-rosette receptor). The involvement of the various cell types reactive to the different monoclonal antibodies in the mitogenic response of swine PBM cells to Con A, phytohemagglutinin (PHA) or pokeweed mitogen (PWM) was investigated by cellular depletion with monoclonal antibody plus complement. Cellular depletion of PBM cells with the following monoclonal antibodies plus complement treatment resulted in: MSA1, almost total reduction in the mitogenic response to low doses of Con A or PWM; MSA2, partial reduction in the proliferative responses to any concentration of Con A, PHA or PWM; MSA3, partial reduction in proliferative responses to low concentrations of Con A or PWM and 4) MSA4, total elimination of any proliferative response to Con A, PHA or PWM.

Animals↗
PubMed1985

Porcine lymphoblastoid cell lines of B-cell origin.

Two lymphoblastoid cell lines were isolated from different pigs and were maintained in culture for over 100 passages or 20 months. These cell lines were characterized by their cell surface antigens, ability to stimulate a mixed lymphocyte reaction and production of immunoglobulin. When tested against a panel of monoclonal anti-cell surface antigen antibodies, only those monoclonal antibodies which detect porcine class I or II molecules reacted against the lymphoblastoid cell lines in a microcytotoxicity assay. The two pig cell lines could stimulate peripheral blood mononuclear cells in a mixed lymphocyte reaction. P-SC(1) and P-16(2) also demonstrated a dependency upon the presence of 2-mercaptoethanol for cell division. The secretion of pig immunoglobulin by P-SC(1) or P-16(2) was first demonstrated by ELISA using a polyclonal anti-swine IgG (heavy and light chain) serum. By the use of monoclonal anti-IgA, IgG or IgM antibodies in an enzyme-linked assay on Western blots of P-SC(1) or P-16(2) lysate/supernatant, the two cell lines were demonstrated to be producing a whole monomeric IgA molecule and a mu chain.

Animals↗
PubMed1985

Quantitation of two-dimensional gel proteins reveals unequal amounts of Tcp-1 gene products during mouse spermatogenesis but no correlation with transmission ratio distortion.

The discovery of a protein, p63/6.9, that is synthesized by both somatic and germ cells and coded for by a gene, Tcp-1, within the t complex provides a molecular probe for examining transmission ratio distortion in t mice. Two electromorphs of this protein exist. The acidic protein (a) is encoded by t-haplotype chromosomes, while the basic protein (b) is encoded by wild-type 17th chromosomes. We have measured the relative amounts of p63/6.9a and p63/6.9b for various t-complex bearing males and for several stages of spermatogenesis. There was no correlation between the ratio of p63/6.9a to b and the magnitude of transmission ratio distortion but the relative amounts of these proteins present in testicular cells can vary depending on the method of labelling. In vivo labelling results in the detection of two-fold greater amounts of p63/6.9a while in vitro labelling produces equimolar amounts of these two proteins. These data suggest that unequal synthesis or degradation of the p63/6.9 proteins occurs during spermatogenesis. It is proposed that increased synthesis of p63/6.9a in vivo is an intrinsic property of t-haplotypes.

Animals↗
PubMed1984

The culturing of pig peripheral blood lymphocytes in microelisa wells for the direct measurement of a specific antibody response.

A simple but sensitive method for measuring the in vitro antibody response of cells from pig peripheral blood to a specific antigen is described. Peripheral blood mononuclear cells from lysozyme immunized pigs are cultured in the presence of lysozyme for five days, then washed and transferred to lysozyme coated wells of a microelisa plate and incubated for 18 hr. After washing the cells off the microelisa wells, the amount of pig anti-lysozyme immunoglobulin produced was measured by an enzyme-linked immunosorbent assay (ELISA). This assay allowed for the monitoring of the appearance of antibody-producing cells in the peripheral blood. In addition, the in vitro response of individual pigs to lysozyme correlated with serum antibody titers to lysozyme but not with the in vitro proliferative response of T cells to lysozyme. The assay provides an in vitro system for studying immunodeficiency in piglets and the general mechanisms behind a low immune response to a specific antigen.

Animals↗
PubMed1984

Monoclonal antibodies to Brucella surface antigens associated with the smooth lipopolysaccharide complex.

Hybridomas producing antibodies to determinants associated with the lipopolysaccharide (LPS) of Brucella abortus and B melitensis were obtained by polyethylene glycol fusion of the SP2/0 myeloma cell line with B lymphocytes harvested from a Sprague-Dawley-derived rat previously immunized with whole B abortus strain 1119 organisms. Two clones, BRU38 and BRU28 , were selected for their ability to react with whole B abortus organisms and purified smooth-LPS ( f5p ). The BRU38 monoclonal antibodies were absorbed with live, rough strain 45/20 and smooth strains of B abortus and B melitensis organisms, whereas only smooth strains absorbed the antibody activity from BRU28 . Complete inhibition of the monoclonal's activity could be achieved with crude smooth-LPS, a purified f5p fraction, and a water-soluble acid degraded polysaccharide. Absorption of BRU38 and BRU28 with rough Brucella LPS, polysaccharide-B antigen, keto- deoxyoctanoic acid, or with several sugars and fatty acids known to be components of the Brucella LPS complex had no effect on the monoclonals. The data indicate that antigenic determinants are associated with the smooth LPS complex, probably with the O-side chain, and are expressed patchwise and in different quantities on several strains of B abortus and B melitensis. The B abortus rough strain 45/20 contains surface determinants which lead to the agglutination of smooth strain 1119 organisms. The potential use of monoclonals in competitive enzyme-linked immunosorbent assays for diagnostic purposes is discussed.

Agglutination Tests↗