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Biomedical subjects

A R Moskovitz

Publications and source records attributed to A R Moskovitz.

16 recordsLinked to original sources
PubMed1998

Comparison of inflammatory events in skin sites with and without cutaneous late-phase reactions after prominent immediate IgE-mediated responses.

BACKGROUND: A number of inflammatory events have been detected in skin chambers overlying sites of developing late-phase reactions (LPR) to pollen antigens in sensitive subjects. However, the pathogenic significance of such events is still unclear. OBJECTIVE: We sought to compare inflammatory responses and cytokine levels in skin chambers that overlie sites of antigen challenge in individuals with and individuals without LPRs after immediate wheal responses of similar intensity. RESULTS: Early histamine releases at antigen sites were similar in eight subjects with LPR (+/+ group) and eight subjects without LPR (+/- group). However, histamine releases during hours 2 through 5 of antigen challenge were significantly greater in the +/+ subjects than in the +/- subjects. Total exuding leukocytes; percent eosinophils; and levels of eosinophil cationic protein, lactoferrin, and IL-8 were significantly greater at antigen versus buffer control challenge sites in both the +/+ and +/- groups, with no significant differences between the groups. IL-1 and IL-6 levels were not greater at antigen sites than at buffer sites. CONCLUSIONS: The only significantly greater antigen-induced response detected in +/+ subjects than in +/- subjects was in later histamine release, which is possibly a marker of other inflammatory responses because histamine itself does not induce LPRs. Other inflammatory events assessed may be somewhat greater in +/+ subjects, but not significantly so.

Antigens↗
PubMed1998

Comparison of inflammatory events during developing immunoglobulin E-mediated late-phase reactions and delayed-hypersensitivity reactions.

To compare cellular and mediator responses in early developing late-phase skin reactions (LPR) and delayed-hypersensitivity (DH) reactions in the same subjects, responses in skin chambers overlying sites of challenge with pollen antigen and Candida albicans antigens were compared in six humans with demonstrated prominent LPR and DH responses. Histamine levels in overlying chamber fluids at 1 h were much higher at LPR than at DH sites (P = 0.002). After the next 4 h, leukocyte exudation was higher at LPR than at DH sites (P = 0.005). Most leukocytes were activated neutrophils with greater frequency of superoxide-secreting cells and released lactoferrin at LPR than at DH sites (P = 0.01 and P = 0.02, respectively). The frequency of exuding eosinophils was higher, but not significantly so (P = 0.5), at LPR sites. Although significantly more eosinophils at LPR sites were activated (P = 0.02), the levels of released eosinophilic cationic protein were not significantly higher at LPR sites (P = 0.09). The levels of interleukin-8 (IL-8), but not IL-6, were greater at LPR than at DH sites. During the first 5 h of challenge there was greater mast cell activation and subsequent exudation of activated neutrophils at sites of developing LPR than at DH sites, possibly related to greater local IL-8 levels. The frequency of activated eosinophils was also greater at LPR sites. These different initial inflammatory responses could play a role in determining expression of LPR or DH reactions.

Allergens↗
PubMed1997

Cytokine levels and inflammatory responses in developing late-phase allergic reactions in the skin.

BACKGROUND: Cytokines could play roles in the attraction of leukocytes into sites of IgE-mediated late-phase reactions (LPR) or in the activation of such cells at the sites. Previous studies found increased release of IL-6, IL-1, and granulocyte-macrophage colony-stimulating factor into skin chambers overlying allergen-challenged sites, mainly after 6 hours when LPR are already well-developed. OBJECTIVE: To compare levels of several cytokines with inflammatory responses in skin chambers overlying developing LPRs. METHODS: Skin chambers were appended to denuded blister bases in 15 sensitive subjects, then challenged over a 5-hour period with pollen allergens (Ag) or buffer control (B). Levels of several chemotactic cytokines, eosinophil cationic product (released from eosinophils), and lactoferrin (released from neutrophils) were measured and leukocyte accumulation was assessed. RESULTS: Levels of the chemokines IL-8, RANTES, and monocyte chemotactic protein-1 (but not IL-1, IL-6, or granulocyte-macrophage colony-stimulating factor) were significantly higher at Ag-challenge sites than at B-challenge sites. IL-5 was not detected. In individual chamber fluids at Ag-challenge sites, (1) IL-8 levels correlated strongly with levels of lactoferrin but not with eosinophil cationic protein levels; (2) RANTES levels correlated with numbers of eosinophils but not with eosinophil cationic protein levels; and (3) levels of monocyte chemotactic protein-1 correlated weakly with histamine released after the first hour. CONCLUSIONS: During LPRs developing during the first 5 hours of Ag challenge, there is increased local release of several chemokines, which could play roles in the observed attraction and subsequent activation of leukocytes and continued histamine release observed at such sites.

Blister↗
PubMed1992

Effects of skin-chamber fluids from human allergic reactions on neutrophil activation.

We have found activated neutrophils (PMNs) in skin chambers overlying the site of ongoing human allergic reactions. To determine whether this activation is due to component(s) released early in these IgE-mediated reactions, we investigated the in vitro effects of skin chamber fluids (CF) on resting blood PMNs. These skin CF had been previously obtained, at different time periods, at pollen-antigen-challenged or buffer-control-challenged sites in sensitive human subjects. PMNs incubated with CF obtained during the first hour of antigen challenge (first-hour CF) generated significantly more superoxide (O2-) than spontaneous production (p less than 0.001) and more than PMNs incubated with first-hour buffer-site CF (p less than 0.002). A pattern similar to O2- generation was observed in lactoferrin secretion during the incubation of the three cell aliquots described above (p less than 0.001). After these incubations, the subsequent responsiveness of the PMNs present in the cell buttons to opsonized zymosan, a PMN activator, was assessed. PMNs previously incubated with first-hour CF generated significantly more net O2- in response to opsonized zymosan than did PMNs previously incubated with first-hour buffer-site CF (p less than 0.001) or buffered saline (p less than 0.001). Again, a similar difference in the patterns of net lactoferrin secretion was observed (p less than 0.02). These events were not associated with PMN damage. Analogous studies with CF previously obtained during the second- to first-hour of antigen or buffer challenge stimulated much less than first-hour CF. We conclude that one or more components released early in IgE-mediated skin reactions can activate PMNs. The nature of the activating component(s) is unknown, with no evidence of activation by histamine, antigen, or other components found to date in first-hour CF.

Adult↗
PubMed1990

Platelet-activating factor- and leukotriene B4-induced release of lactoferrin from blood neutrophils of atopic and nonatopic individuals.

We found increased accumulation of neutrophils and their components, lactoferrin (Lf) and elastase, as well as platelet-activating factor (PAF) and leukotriene B4 (LTB4) at sites of ongoing human allergic reactions. To determine whether PAF or LTB4, could be the stimulus for in vivo Lf release, blood neutrophils of 17 subjects were incubated with PAF, LTB4, or the phorbol ester, phorbol myristate acetate (PMA), and the released Lf (ELISA assay) was compared with spontaneous release. Significantly increased Lf release was induced by PAF, 10(-5) to 10(-8) mol/L (p less than 0.002); LTB4, 10(-7) to 10(-8) mol/L (p less than 0.004); and PMA (0.05 micrograms/ml) in a dose-dependent reaction. Cytochalasin was not required for Lf secretion but did enhance such responses. PAF-induced Lf secretion was inhibited by the specific PAF antagonist, BN 52063. More Lf was released from neutrophils of atopic than from nonatopic subjects in response to PAF, 10(-6) mol/L (4.2 micrograms/ml +/- 0.2 versus 2.6 micrograms/ml +/- 0.2; p less than 0.001) but not to LTB4, PMA, or buffer (p, not significant). We conclude that (1) PAF and LTB4 released in vivo could stimulate local neutrophils to release Lf with possible pathogenic effects and (2) neutrophils of atopic subjects are more responsive to PAF than neutrophils of nonatopic subjects in this regard.

Adult↗
PubMed1986

Suppressor T cells in myasthenia gravis and antibodies to acetylcholine receptor.

We cultured blood mononuclear cells of patients with myasthenia gravis both with and without removal of T8 suppressor cells. The levels of synthesized antibodies to acetylcholine receptor and IgG as well as the frequency of immunoglobulin-secreting cells were all higher in pokeweed mitogen-stimulated cultures depleted of T8+ cells. Thus, autologous suppressor cells within the T8+ population exert some regulatory control over antiacetylcholine receptor-producing cells in patients with myasthenia gravis.

Adult↗
PubMed1985

Circulating T-cell subsets in Guillain-Barré syndrome.

We compared the distribution of circulating T-cell subsets within 2 weeks of onset of symptoms in 14 patients with acute Guillain-Barré syndrome (GBS) and 37 normal controls. The levels of OKT4+ (putative helper-inducer) cells was definitely abnormal (decreased) in 3/13 tested. The levels of OKT8+ (putative suppressor-cytotoxic) cells were elevated in 3 and decreased in 2 of the 14 tested. Abnormal OKT4/OKT8 ratios were detected in 5 (2 elevated and 3 decreased) patients. Four of the 5 GBS patients with abnormal OKT4+/OKT8+ ratios were studied sequentially at least 4 times over 1-10 months; there was a return towards a normal ratio in all. Serial studies in 3 other GBS patients showed consistently normal values. In comparison, sequential studies over 5-24 months in 7 normals showed no abnormal OKT4+/OKT8+ ratios. Thus, abnormalities in OKT4+/OKT8+ ratios appear to be a marker of systemic events during symptomatic phases of GBS. It is not as yet known whether this is related to the cause or is secondary to the clinical manifestations of GBS.

Antibodies, Monoclonal↗
PubMed1984

Thymic B-cell activation in myasthenia gravis.

We studied secretion of immunoglobulin (Ig) by freshly isolated and pokeweed mitogen (PWM)-stimulated thymus cells and blood mononuclear cells in patients with myasthenia gravis (MG) and control subjects undergoing elective cardiac surgery. We used a protein A reverse hemolytic plaque assay to enumerate cells secreting IgG, IgM, and IgA (IgSC), and an ELISA assay for measuring IgG secreted into culture supernatants. We found that freshly isolated suspensions of MG thymus cells, compared with control thymus cells, contained increased numbers of cells that spontaneously secreted immunoglobulin. Thymus mononuclear cells from control as well as MG patients appeared capable of B-cell differentiation responses when stimulated by PWM. PWM-induced responses were greater in thymic than in autologous blood mononuclear cells in some MG patients and controls, although B cells were much less frequent in suspensions of thymic cells than blood cells. Thus, the thymus provides a favorable milieu for differentiation of its few B cells. In MG, the thymus may be a site of accentuated in vivo B-cell activation, as evidenced by increased numbers of resident IgSC.

Adolescent↗
PubMed1984

In vitro synthesis of antibodies to acetylcholine receptor by peripheral blood cells: role of suppressor T cells in normal subjects.

Peripheral blood mononuclear cells of 15 of 20 patients with generalized myasthenia gravis synthesized antibodies to acetylcholine receptor (AChR) when the cells were stimulated in vitro with pokeweed mitogen. In contrast, mononuclear cells of 1 of 16 normal subjects synthesized detectable AChR antibodies. Peripheral blood mononuclear cells of five normal subjects were studied before and after putative suppressor T cells (OKT8+) were removed by a fluorescent activated cell sorter. Depletion of OKT8+ cells did not result in production of AChR antibodies, but pokeweed mitogen-induced polyclonal IgG synthesis and activation of B cells to form immunoglobulin-secreting cells (reverse hemolytic plaque assay) were increased. Therefore, failure of blood mononuclear cells of normal subjects to synthesize detectable anti-AChR in response to pokeweed mitogen is not due to suppression by OKT8+ cells.

Antibody Formation↗
PubMed1983

Analysis of B-cell activation of cerebrospinal fluid lymphocytes in multiple sclerosis.

We have developed a microculture system to study pokeweed mitogen (PWM)-induced B-cell differentiation responses of CSF lymphocytes from patients with multiple sclerosis (MS) and other neurologic diseases (OND). B-cell differentiation was assessed by (1) enumeration of immunoglobulin-secreting cells (IgSC) by a protein A reverse hemolytic plaque assay; and (2) quantitation of supernatant IgG by ELISA. Cultures of MS CSF cells and OND CSF cells responded to PWM with a similar frequency, with responses in CSF cell cultures exceeding responses in corresponding blood cell cultures in several instances in both groups of patients. Numbers of IgSC in unstimulated cultures of MS CSF cells exceeded numbers in cultures of autologous peripheral blood mononuclear cells (PBM). Results suggest that CSF cells may be a particularly reactive population compared with PBM.

B-Lymphocytes↗
PubMed1983

Immune reactions to P2 protein in human inflammatory demyelinative neuropathies.

The significance of immune reactions against peripheral nervous system antigens in the human inflammatory polyneuropathies is still uncertain. Using a very sensitive assay, we found greatly increased levels of anti-P2 antibodies in sera of animals with experimental allergic neuritis (EAN) but no increases in humans with acute Guillain-Barré syndrome (GBS), chronic relapsing polyneuritis (CRIP), axonal neuropathy, or normals. P2 protein and CNS basic protein did not induce any increased proliferation in lymphocytes of GBS or CRIP patients. We conclude that P2 and BP appear unlikely to be targets for humoral or cellular immune reactivity in GBS or CRIP.

Adolescent↗
PubMed1983

Thymic lymphocyte subpopulations in myasthenia gravis.

We compared the percentages of thymic mononuclear cells (TMC) that bind monoclonal antibodies to T-cell subpopulations in patients with myasthenia gravis (MG) and non-MG patients undergoing cardiac surgery (CS). There were no significant differences in percentages of OKT3+, OKT4+, OKT6+, or OKT8+ cells or the OKT4:OKT8 ratio. There was an increase in the percentage of Ia+ (immune response gene-associated antigen) TMC in MG compared with CS but no significant differences in B cells or phagocytic cells. The Ia+ cells could be abnormal B cells, activated T cells, or thymic dendritic cells.

Adult↗
PubMed1982

Antibodies to P2 and P1 myelin antigens in experimental allergic neuritis and allergic encephalomyelitis.

We confirmed earlier observations that experimental allergic neuritis (EAN) in Lewis rats induced by injection of bovine peripheral nerve myelin in complete Freund's adjuvant is not accompanied by development of experimental allergic encephalomyelitis. However, sera of these animals contained elevated titers of antibodies against central nervous system myelin basic protein (BP), likely induced by peripheral nerve P1 protein. Anti-BP antibodies were not seen in sera of rats with EAN induced by peripheral nerve P2 protein. Lack of encephalogenicity of bovine myelin in Lewis rats does not reflect simply lack of immune responses induced against BP.

Animals↗
PubMed1981

Polyclonal B-cell activity in myasthenia gravis.

Using a protein A-reverse hemolytic plaque assay, we found that some patients with myasthenia gravis have increased numbers of circulating immunoglobulin secreting cells (IgSC). This pattern was not related to drug therapy, age, sex, duration of symptoms, thymectomy, or serum levels of AChR antibody, although elevated IgSC values tended to occur in patients with active symptoms. The responses of peripheral blood mononuclear cells to pokeweed mitogen were normal. These data suggest increased in vivo polyclonal B-cell activation in some myasthenic patients, although in vitro polyclonal B-cell activation is normal.

Acetylcholine↗