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Biomedical subjects

B Zweiman

Publications and source records attributed to B Zweiman.

At least 73 records · Page 4Linked to original sources
PubMed1989

Identification of leukotriene B4 as the neutrophil chemotactic factor released by antigen challenge from passively sensitized guinea pig lungs.

Neutrophils are prominent in some IgE-mediated allergic reactions and may contribute to the pathophysiology of immediate hypersensitivity. Antigen challenge of fragments of guinea pig lung tissue that were passively sensitized with IgE or IgG antibody evoked the release of neutrophil chemotactic activity (NCA) in parallel with histamine. The NCA released from lung tissue by both IgG- and IgE-dependent stimulation coeluted from a column of Sephacryl S-300 with synthetic leukotriene B4 (LTB4). The NCA in eluates from the Sephacryl S-300 column contained LTB4, as determined by high-performance liquid chromatography and specific radioimmunoassay, in quantities that accounted for the observed chemoattractant activity in the eluates. Furthermore, the NCA of supernatants from antigen-challenged lung fragments was reduced by a mean of 80% after absorption with a monoclonal antibody to LTB4. LTB4 thus constitutes the major functional constituent of NCA released after anaphylactic challenge of IgE- and IgG-sensitized guinea pig lung tissue.

Anaphylaxis↗
PubMed1988

Release of histamine and tryptase in vivo after prolonged cutaneous challenge with allergen in humans.

The patterns of in vivo release of histamine and tryptase were determined during prolonged Ag incubation in atopic individuals, using skin chambers placed over denuded skin blister sites. However, the patterns of histamine and tryptase release over a period of up to 9 h of Ag exposure were different. Whereas rates of release of both histamine and tryptase peaked within 1 h in an Ag dose-response fashion, that of tryptase decreased progressively thereafter and was not different from buffer challenge sites from the 5th to 9th h at all concentrations of Ag tested. The rate of histamine release reached a plateau after 2 h and remained at a constant low level throughout the 3rd to 9th h of Ag incubation. Rechallenge of the sites continuously exposed to Ag with a different second Ag at the 6th h resulted in a second peak of release of both histamine and tryptase. This persistence of in vivo histamine but not tryptase release during the later time points of the cutaneous allergic response differs from what has been demonstrated in vitro with dispersed mast cells. Whether this reflects basophil participation at these time points or an as yet undetermined mechanism for release of histamine but not tryptase by mast cells is not known. These novel patterns of mediator release after prolonged Ag exposure in vivo may have clinical relevance to allergic diseases during which atopic subjects are exposed to Ag over several hours to days.

Adult↗
PubMed1988

Platelet activating factor increases expression of complement receptors on human neutrophils.

The phospholipid inflammatory mediator platelet activating factor (PAF) has been shown to stimulate certain functions of polymorphonuclear leukocytes (PMN). However, the effect of PAF on surface complement receptors of PMN has not been described. Using monoclonal antibodies and flow cytometry, we have assessed the effects of PAF on surface expression of membrane receptors for C3bi (CR3) and C3b (CR1) in human PMN. PAF (optimal concentration of 1 x 10(-8) M) increased CR3 190% and CR1 174% compared with unstimulated cells at 37 degrees C, while the PAF analogue lyso-PAF had no stimulatory effect. Both CR3 and CR1 responses to PAF reached maximum levels at 15-30 min. PAF effects were comparable to peak effects induced by LTB4 but less than induced by FMLP. A PAF receptor antagonist, SRI 63-441, blocked the increased complement receptor expression in a dose-dependent manner with maximal inhibition of 80-95% at 5 x 10(-6) M. Extracellular calcium had no effect on CR1 expression but slightly enhanced and EGTA partially inhibited the PAF-induced increase in CR3 expression. Simultaneous incubation with PAF and LTB4 enhanced CR3 and CR1 expression more than either agent alone. These findings indicate that PAF, alone and in combination with LTB4, can induce altered expression of complement receptors on the surface of PMN. This effect may enhance adhesion and phagocytosis by PMN at inflammatory reaction sites.

Calcium↗
PubMed1988

Cytotoxic effect of myelin basic protein-reactive T cells on cultured oligodendrocytes.

To help clarify effector mechanisms in experimental allergic encephalitis (EAE), the cytotoxic effects of myelin basic protein (MBP)-reactive lymphocytes on oligodendrocytes were studied using a 51Cr release assay. MBP-reactive encephalitogenic T cell lines were cytotoxic to 51Cr-labeled oligodendrocyte target cells derived from Lewis rat fetal brain-dissociated culture, when incubated for 6 h in the presence of antigen-presenting cells (APC) and MBP (percent 51Cr release = 65 +/- 3% vs. spontaneous release = 22 +/- 3% vs. normal lymph node cells + APC and MBP = 20 +/- 3%). This reaction is time dependent, likely MHC restricted, and is not just a nonspecific toxic effect against any Lewis target cells since neither fibroblasts nor astrocytes were affected. Other (tetanus toxoid-reactive) lymphoblasts stimulated by specific antigen were not cytotoxic to the oligodendrocytes. These findings suggest that oligodendrocytes might be target cells for MBP-reactive lymphocytes in EAE if antigen presentation is appropriate.

Animals↗
PubMed1988

Neurologic complications of collagen vascular diseases.

Despite the importance of neurologic manifestations of the collagen vascular diseases, it is clear that there are more questions than answers. The use of in vitro culture systems, in vivo models, and clinical and laboratory study of patients that attempt to correlate these findings with immunologic abnormalities, including parallels with animal models, should increase our understanding of these syndromes.

Antibodies↗
PubMed1988

Late onset reactions in humans: correlation between skin and bronchial reactivity.

We carried out sequential measurements of the intensity of simultaneously occurring late onset skin and bronchial reactivity in seven atopic subjects following skin and inhalation challenge with pollen antigen. All subjects demonstrated dual bronchial and cutaneous reactions. Although the intensity of the late onset bronchial responses correlated temporally and quantitatively with the degree of increase in serum neutrophil chemotactic activity, the intensity of the late onset skin responses correlated with the level of specific antigen-IgE in the serum. This suggests that even in the same subjects, different factors govern the intensity of late onset skin and bronchial responses.

Bronchial Provocation Tests↗
PubMed1987

Activation of plasma Hageman factor and kallikrein in ongoing allergic reactions in the skin.

Ten atopic subjects, sensitive to intradermal injection of less than or equal to 10 protein nitrogen units of ragweed or grass pollen antigen, underwent paired antigen and buffer skin chamber incubation over the base of denuded skin blisters. The chamber fluids were sampled over a 6-hr period for histamine and activated Hageman factor and plasma kallikrein which were complexed to C1 inhibitor. In 9 of 10 subjects significantly (p less than 0.01) increased histamine levels (74 +/- 11 ng/ml vs 1.5 +/- 0.55 ng/ml) and kallikrein-C1 inhibitor complexes (2.15 +/- 0.78 ng/ml/hr vs 0.51 +/- 0.09 ng/ml/hr, p less than 0.25) were detected at antigen sites compared with buffer sites, respectively. Increased levels of activated Hageman factor (ng/ml/hr) were detected at antigen sites (1.35 +/- 0.60) compared with buffer sites (0.11 +/- 0.05), (p less than 0.01), in 8 of 10 subjects. Whereas peak levels of histamine were obtained after 1 hr of challenge, both Hageman factor and kallikrein activation, as assessed by complex formation, tended to peak later from the 2nd to the 5th hr. This represents the first demonstration that cutaneous IgE-mediated allergic responses are associated with local activation of the intrinsic plasma coagulation-kinin pathways.

Adult↗
PubMed1987

Increased expression of CR3 (C3bi receptor) on neutrophils in human inflammatory skin reactions.

To help determine whether the neutrophils (PMN) found in skin inflammatory reactions are activated, we have compared the expression of the C3bi receptor (CR3) on such cells with that on autologous blood PMN in 10 pollen-sensitive subjects. Using skin chambers overlying denuded blister bases we collected PMN at 2 or 4 hr at sites of challenge with pollen antigen or buffer solution. These cells and PMN in autologous blood were incubated with monoclonal anti-CR3 antibody and the expression of CR3 was measured by indirect fluorescence and flow cytometry. Significantly more PMN were found at antigen than at buffer sites at 2 hr (7.02 +/- 0.45 X 10(5) vs 0.71 +/- 0.25 X 10(5] and at 4 hr (2.2 +/- 0.57 X 10(6) vs 5.47 X 10(5). The mean CR3 expressions on PMN at antigen and buffer sites were similar (117 +/- 7.4 vs 118 +/- 9.0); both were significantly greater than on blood PMN (17.6 +/- 1.5; P less than 0.005). PMN from both sites could be stimulated further in vitro with formyl-methionyl-leucyl-phenylalanine (FMLP) to express more CR3 to a level even greater than in FMLP-stimulated blood PMN (155 +/- 11 and 157 +/- 12, respectively, vs 108 +/- 7 in blood PMN). The incubation of blood PMN with the noncellular component of the chamber fluid led to a moderate (28-100%) increase in CR3 expression, but far less than the CR3 expression on the chamber fluid PMN themselves. Since surface CR3 is thought to be an activation marker important in PMN adhesion, these findings may be important in understanding the emigration of PMN in skin inflammatory reactions.

Adult↗
PubMed1987

Limiting dilution analysis of the frequency of antigen-reactive lymphocytes isolated from the central nervous system of Lewis rats with experimental allergic encephalomyelitis.

Lymphocytes were isolated from the spinal cord and draining lymph nodes of Lewis rats with acute experimental allergic encephalomyelitis (EAE) 12 days after immunization with myelin basic protein (MBP) and tetanus toxoid (TT). An average of 8.0 +/- 2.0 X 10(6) cells was obtained from the spinal cord. Of these 71.1 +/- 8.6% expressed the helper-T-cell marker W3/25 and 14.8 +/- 6.2% expressed the killer/suppressor-T-cell marker OX8. By limiting dilution analysis of cells exhibiting an antigen-specific proliferative response, the average frequencies of cells reactive to MBP and TT were 3.36 +/- 2.4 and 7.60 +/- 4.1 per 10(4), respectively. In the draining lymph nodes, the frequencies of cells reactive to MBP and TT were 2.24 +/- 1.7 and 2.69 +/- 2.5 per 10(4). At a relatively early stage of clinical EAE, MBP-reactive T cells comprise only a small minority of the cells which can be isolated from the spinal cord; lymphocytes reactive to a protein antigen irrelevant to EAE pathogenesis are present in comparable numbers. This finding suggests that most of these cells accumulate as a result of mechanisms not specific for MBP-reactive lymphocytes.

Animals↗
PubMed1987

Cellular inflammatory responses in human allergic skin reactions.

To define better the role of inflammation in the response to pollen antigens, we have used our skin chamber model to study inflammatory cells recovered from the sites of ongoing allergic reactions. In 15 atopic subjects, paired skin blister sites were simultaneously challenged with ragweed- or grass-pollen antigen or buffer for 5 hours. There were 10 times as many cells recovered at antigen (20.7 X 10(5)) than at buffer (2.0 X 10(5)) sites, p less than 0.005; greater than 97% of the cells recovered were neutrophils. The number of cells recovered at the antigen sites correlated with the total amount of histamine released (r = 0.57; p less than 0.05) but not with the extinction dilution skin test reactivity nor with the intensity of the late cutaneous allergic response measured 6 hours after the injection of antigen. Phase-contrast microscopic examination of the cells recovered from the antigen sites demonstrated that 82% to 95% were polarized compared to 0% to 1.5% of autologous blood neutrophils obtained simultaneously from the peripheral blood. Antigen site cells were as capable of serum-dependent phagocytosis as peripheral blood neutrophils. There was no significant difference in the migratory response to buffer, the chemoattractant N-formyl-methionyl-leucyl-phenylalanine, or leukotriene B4, but there was a significantly decreased response to platelet-activating factor when the cells recovered from antigen sites were compared to autologous blood neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗