PubMed Health⌕ Search

Biomedical subjects

M A Vadas

Publications and source records attributed to M A Vadas.

At least 181 records · Page 10Linked to original sources
PubMed1982

Bullous pemphigoid blister fluid stimulates eosinophil colony formation and activates eosinophils.

An eosinophil stimulating material (ESM) is described in the blister fluids (BF) of six patients with bullous pemphigoid (BP). This ESM is similar in function to a subspecies of human colony stimulating factor (CSF), CSF-alpha, since (i) it stimulated the production from bone marrow cells of day 14 colonies (31 +/- 15, arithmetic mean +/- 1 s.e.m. colonies, n = 5) in semi-solid agar, (ii) a large proportion (47 +/- 12%, n = 5) of these colonies were eosinophilic and (iii) it activated purified peripheral eosinophils as judged by increased autofluorescence (a mean increase of 23.6 +/- 6.6 units measured by flow cytometry, n = 10). BF from patients with four other blistering diseases, burn blisters, suction blisters from normal, eosinophilic or BP patients, various sera, histamine and eosinophil chemotactic factor (ECF-A) lacked activities in these assays. This description of a tissue accumulation of a CSF like substance suggests that there exists a physiological role for CSF in the periphery. In addition it supports the concept that local activation of eosinophils contributes to the pathogenesis of BP.

Aged↗
PubMed1982

Genetic control of eosinophilia in mice: gene(s) expressed in bone marrow-derived cells control high responsiveness.

A heterogeneity in the capacity of strains of mice to mount eosinophilia is described. BALB/c and C3H are eosinophil high responder strains (EO-HR) and CBA and A/J are eosinophil low responder strains (EO-LR), judged by the response of blood eosinophils to Ascaris suum, and the response of blood, bone marrow, and spleen eosinophils to keyhole limpet hemocyanin given 2 days after 150 mg/kg cyclophosphamide. Some of the gene(s) for high responsiveness appear to be dominant because (EO-HR X EO-LR)F1 mice were intermediate to high responders. This gene is expressed in bone marrow-derived cells because radiation chimeras of the type EO-HR leads to F1 were high responders and EO-LR leads to F1 were low responders. This description of a genetic control of eosinophilia in mice may be useful in understanding the role of this cell in parasite immunity and allergy.

Animals↗
PubMed1981

Immune evasion by Schistosoma mansoni: loss of susceptibility to antibody or complement-dependent eosinophil attack by schistosomula cultured in medium free of macromolecules.

Schistosomula of Schistosoma mansoni, recovered either after penetration of cercariae through isolated rat skin or by mechanical transformation of cercariae, become fully resistant after 24-48 h of culture to damage by human blood eosinophils in the presence of human anti-schistosomular sera. Cultured schistosomula are also shown to lose their susceptibility to attack by human eosinophils in the presence of human complement. This resistance is related to the simultaneous reduction of the ability of human anti-schistosomular antibodies and human complement component C3 to bind to the surface of the cultured larvae. The development of insusceptibility to antibody, complement and eosinophil-mediated attack does not require the acquisition by the schistosomula of a protective coat of host or other macromolecules, since it is achieved in chemically defined culture medium free of serum and macromolecules. This supports the hypothesis that schistosomula undergo intrinsic changes which render them insusceptible to immune attack.

Animals↗
PubMed1981

An autoantibody reactive with nuclei of polymorphonuclear neutrophils: a cell differentiation marker.

An autoantibody that reacted with nuclei of polymorphonuclear neutrophils (PMN) was detected at titers of greater than 10 in sera of 25 of 50 patients with rheumatoid arthritis and 36 of 50 with autoimmune chronic active hepatitis but in none of 160 controls comprising 24 patients with alcoholic cirrhosis, 36 with multiple myeloma, and 100 healthy subjects. Through the use of enriched populations of hemopoietic cells, this antibody was shown to be cell-specific, reacting only with the nucleus of the mature neutrophil. It was unreactive with nuclei of progenitor cells in the myeloid series and with nuclei of eosinophils, monocytes, lymphocytes, and thymocytes. It reacted with a determinant that appeared to be a differentiation antigen. This cell-specific autoantibody may prove to be of value in analytical studies of granulocyte maturation.

Antibodies, Antinuclear↗
PubMed1981

Cyclophosphamide pretreatment induces eosinophilia to nonparasite antigens.

Eosinophilia is usually regarded as a T cell-dependent hemopoietic response, although in most instances of immune responses by T cells there is no accompanying eosinophilia. BALB/c mice immunized with keyhole limpet hemocyanin (KLH) in complete Freund's adjuvant (CFA) were found not to develop eosinophilia, whereas pretreatment of such mice with 150 mg/kg cyclophosphamide (CY) induced marked eosinophilia in the blood (1000 to 3000/mm3) and bone marrow. CY as well as CY and KLH in CFA cause a leukocytosis and neutrophilia, but significant eosinophilia was seen only in mice receiving both CY and KLH-CFA. The eosinophilic response depended on the dose of CY and peaked 13 days after immunization, and was preceded by a bone marrow eosinophilia that peaked 8 days after immunization. No eosinophilia occurred in BALB/c nu/nu mice after CY and KLH-CFA but did occur in the nu/+ littermates. This model in mice of eosinophilia in response to CY followed by a nonparasite antigen should be useful in the analysis of T cell signals that might regulate eosinophilia.

Animals↗
PubMed1980

Enhanced helminthotoxic capacity of eosinophils from patients with eosinophilia.

To determine whether eosinophils from patients with eosinophilia have an enhanced capacity to kill parasites, we compared purified eosinophils (mean purity, 89 per cent) from 30 patients with various degrees of eosinophilia and with or without infection with Schistosoma mansoni for the capacity to kill schistosomula, the larval stage of S. mansoni, in vitro. There was a significant correlation between peripheral eosinophil count and antibody-dependent, eosinophil-mediated death of parasites after 40 hours of culture (P < 0.0001). Antibody-dependent adherence of eosinophils, measured after two hours of incubation, also correlated with the capacity of the eosinophils to kill the parasites. The correlation between the killing capacity of eosinophils and their peripheral-blood count was observed in patients both with and without S. mansoni infection. We suggest that eosinophilia involves not only a quantitative change in eosinophil numbers but also a qualitative change in functional capacity that renders circulating eosinophils more effective in resisting parasitic infections.

Antibodies↗
PubMed1980

Parasite immunity and the major histocompatibility complex.

Parasite infestations offer fertile ground for investigation of the relationship between immunity, disease and the major histocompatibility complex (MHC). However, due to the complexities of parasite life cycles and the success of parasites in evading the immune response, immune reactions against the parasite often do not parallel protective immunity, and immunity does not imply lack of disease. -- An additional level of complexity is introduced in some forms of parasite immunity by accessory effector cells, e.g., macrophages and eosinophils, that need to be 'activated' for maximal effectiveness, and the 'activated' form of these cells may partly compensate for a deficiency in specific immune responses. -- It is not surprising, therefore, that polygenic effects operate in parasite immunity and reports linking non-MHC genes with parasite immunity far out number those linking MHC genes with it. From the reports that do link MHC genes with parasite immunity, two areas emerge that are interesting. First, the increased incidence of certain HLA genes in people with schistosomiasis who develop hepatosplenic disease may pinpoint individuals at risk of morbidity and direct early treatment to them. Second, mechanisms that intimately involve MHC products but are not linked to a particular MHC haplotype, may indicate newer areas in the investigation of parasite immunity.

Animals↗
PubMed1980

Mechanism of the interaction mediating killing of Schistosoma mansoni by human eosinophils.

Recent work on the role of eosinophils in immunity to Schistosoma mansoni is summarized. In vitro studies have shown that human eosinophils can kill antibody-covered schistosomula. The killing mediated by eosinophils is associated with adherence of these cells and subsequent degranulation and release of eosinophil major basic protein onto the larvae. The major basic protein itself can kill the larvae. Antibody-dependent eosinophil adherence to the larvae proceeds in at least two distinct steps. The first is mediated by Fc receptors and is relatively weak; the second is a temperature-dependent step which allows a firm irreversible binding of eosinophils to schistosomula. This stable binding is associated with degranulation of eosinophils, a process which appears to contribute to the preferential capacity of this cell to mediate antibody-dependent damage to schistosomula.

Animals↗
PubMed1980

Functional studies on purified eosinophils and neutrophils from patients with Schistosoma mansoni infections.

Unpurified peripheral blood leucocytes or purified eosinophils and neutrophils from patients with schistosomiasis and from normal individuals were compared for their ability to interact with antibody coated schistosomula of Schistosoma mansoni. There was no difference in the ability of buffy coat cells or neutrophils from patients and from normal individuals to mediate antibody-dependent 51Cr release from labelled schistosomula. However, eosinophils from patients were significantly better than those from normal individuals in causing antibody-dependent 51Cr release. This enhanced activity of eosinophils from patients with schistosomiasis was found to correlate with the intensity of their infection as judged by faecal egg counts. Eosinophils from patients also contained a higher proportion of cells with detectable Fc receptors than those from normal individuals. It is suggested that the difference in the behaviour of eosinophils from patients and from normals may reflect an 'activated' state of these cells in the infected individuals.

Adolescent↗
PubMed1979

Interactions between human eosinophils and schistosomula of Schistosoma mansoni. II. The mechanism of irreversible eosinophil adherence.

Previous work (1)(1) has shown that normal human eosinophils show a preferential capacity, in comparison with neutrophils, to bind to antibody- coated schistosomula of Schistosoma mansoni. This effect is attributable to a temperature-dependent function of the eosinophil which renders its binding stable and irreversible by aggregated gamma globulin or Staphylococcus aureus protein A. In contrast, the binding of neutrophils is readily reversible by these agents. It has now been shown that the differences observed between eosinophils and neutrophils is a property of their interaction with living schistosomula. When dead or artificially damaged schistosomula were tested, neutrophils showed a markedly enhanced capacity to adhere, in both the presence and absence of anti-chistosomular serum. Subsequent experiments were designed to test the hypothesis that the strong, stable binding of eosinophils was attributable to degranulation, with release of granule contents which would then serve as ligands to bind the cell to the organism. First, an enhanced adherence both of eosinophils and of neutrophils could be demonstrated in the presence of eosinophil major basic protein (MBP) or of protamine, a high molecular weight cation. Second, the binding of eosinophils induced by concanavalin A (Con A) was found to differ markedly from that induced by antischistosomular serum. Con A-mediated binding of eosinophils was fully reversible by alpha-methyl-mannoside, was not associated with damage to the organism, and did not lead to degranulation of the cell, as estimated by measuring the release of MBP into the culture supernate. However, induction of degranulation of concanavalin A-bound eosinophils, but not of neutrophils, with the calcium ionophore A23187 converted the reaction into one which was no longer reversible by alpha- methylmannoside and in which damage to the organism now did occur. These findings support the hypothesis that the stable binding of eosinophils is associated with degranulation, a process which may contribute to the preferential capacity of this cell to mediate antibody-dependent damage to schistosomula.

Antibodies↗
PubMed1979

Major histocompatibility complex products restrict the adherence of cytolytic T lymphocytes to minor histocompatibility antigens or to trinitrophenyl determinants on schistosomula of Schistosoma mansoni.

We have previously shown that schistosomula passaged through mice acquire histocompatibility (H) antigens that can be recognized either by alloantibody or by alloreactive cytolytic T lymphocytes (CTL). The latter specifically adhere to but fail to damage the parasite. In this paper we describe the use of trinitrophenyl (TNP)-labeled schistosomula to show that the adherence of CTL with specificity for TNP-modified syngeneic cells is restricted by the major histocompatibility complex (MHC) in a fashion similar to that seen in the lysis of TNP-labeled tumor targets. Thus, these CTL adhere only to schistosomula that have both the appropriate H antigens and TNP determinants on their surface, and not to schistosomula bearing either of these antigens by themselves. We note a significant degree of adherence to schistosomula bearing TNP determinants and H antigens allogeneic to the CTL. Anti-minor H antigen CTL are also restricted by the MHC in their adherence; thus, they only adhere to schistosomula that carry both the major and minor H antigens of the stimulator cells. These antigens can be acquired either by a single passage in vivo of schistosomula through congenic strains that possess both the relevant antigens or by sequential passage through two different strains, each contributing one of the antigens in question.

Animals↗