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Biomedical subjects

G M Walsh

Publications and source records attributed to G M Walsh.

At least 55 records · Page 3Linked to original sources
PubMed1996

Integrin alpha 4 beta 7 mediates human eosinophil interaction with MAdCAM-1, VCAM-1 and fibronectin.

We have investigated the contribution of integrin alpha 4 beta 7 to human peripheral blood eosinophil adhesive interactions. Immunofluorescence and flow cytometry demonstrated constitutive expression of alpha 4 beta 7 by eosinophils. Expression of alpha 4 beta 7 or alpha 4 beta 7 was not enhanced by eosinophil activation with platelet-activating factor (PAF). Expression of alpha 4 beta 7 was confirmed by immuno-precipitation of 125I-labeled lysates analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE). Approximately 20% of unstimulated eosinophils were adherent to L1-2 cells transfected with vascular cell adhesion molecule-1 (VCAM-1) cDNA, while very few resting eosinophils adhered to mouse mucosal adressin cell adhesion molecule-1 (MAdCAM-1) transfectants. Binding of unstimulated eosinophils to VCAM-1 transfectant was inhibited by HPI 2 (an antibody that blocks both alpha 4 beta 1 and alpha 4 beta 7 functions), but not Act-1, and alpha 4 beta 1 monoclonal antibody (mAb). PAF stimulation resulted in increased binding of eosinophils to MAdCAM-1 transfectants, which was inhibited by both HPI 2 and Act-1. In contrast, PAF did not enhance binding to VCAM 1 transfectants, although binding of PAE-stimulated eosinophils to VCAM-1 could be partially inhibited by Act-1. Stimulation of eosinophils with the beta 7-activating mAb TS2 16 resulted in enhanced binding of eosinophils to both VCAM-1 and MAdCAM-1 transfectants. The increased binding was largely alpha 4 beta 7-dependent. Unstimulated eosinophils bound to soluble recombinant human (rh) VCAM-1 and fibronectin (Fn), coated on 96-well plates in dose-dependent manner. Binding was inhibited by HPI-2 and 4b4, an anti-beta 1 mAb, but not by Act-1. TS2 16 treatment increased adherent cell numbers and this enhanced binding was inhibited by Act-1. We have therefore confirmed that alpha 4 beta 7 is functionally active on unstimulated eosinophils. In contrast, PAF-induced enhancement of eosinophils binding to VCAM-1 or MAdCAM-1 was alpha 4 beta 7-dependent. In addition treatment with TS2 16 resulted in a alpha 4 beta 7-dependent enhancement of eosinophil binding to VCAM-1, MAdCAM-1 and Fn. We therefore hypothesize that alpha 4 beta 7 may have an important role in eosinophil localization in diseases such as asthma and inflammatory bowel disease.

Cell Adhesion↗
PubMed1995

Human eosinophils preferentially survive on tissue fibronectin compared with plasma fibronectin.

BACKGROUND: Eosinophil-derived inflammatory mediators including cytokines are considered to be important in the pathogenesis of allergic inflammation. Fibronectin (Fn) has been shown to be a physiological trigger of autocrine cytokine production by human eosinophils. Fn is encoded by a single gene, but alternate splicing of the primary RNA transcript results in polypeptide diversity in a cell type-specific fashion. Thus, tissue Fn contains approximately 50% more of the CS-1 cell binding region recognized by the integrin alpha 4 beta 1 compared with plasma Fn. OBJECTIVE: Since eosinophils are predominantly tissue-dwelling cells we compared the effect of tissue and plasma Fn on eosinophil survival in culture. METHODS: The viability and cytokine generation of eosinophils (> 99.9% pure) cultured for up to 4 days in 96 well plates coated with tissue Fn, plasma Fn or BSA was compared. RESULTS: There was a significant difference in the ability of tissue Fn to support eosinophil survival compared with plasma Fn (P < 0.01). Optimal survival with tissue Fn was seen at 25 micrograms/well (70% +/- 2.0% viability at 3 days vs 7% +/- 2.2% viability on BSA). Significant (P < 0.001) cell viability on tissue Fn was observed for up to 4 days in culture (54% +/- 6.0%) compared with BSA coated wells. Addition of autologous mononuclear cells (final concentration 0.5%, 1% or 2%) resulted in plasma Fn-dependent eosinophil survival comparable to that of 99.9% pure eosinophils adherent to tissue Fn. Tissue Fn-dependent survival was significantly inhibited by anti-interleukin-3, anti-granulocyte macrophage colony stimulating factor (GM-CSF) and anti-IL-5 monoclonal antibodies. Picogram quantities of these three cytokines were detected in supernatants from eosinophils cultured for 3 days on tissue Fn using specific enzyme-linked immunosorbent assays (ELISAs). Eosinophil survival on tissue Fn was significantly inhibited by anti-beta 1 and alpha 4 beta 1 monoclonal antibody (MoAb) and also by a MoAb specific for the CS-1 motif in the IIICS region of Fn. CONCLUSION: These observations show preferential survival of eosinophils cultured on tissue Fn as a result of alpha 4 beta 1-dependent interaction with the CS-1 region of tissue Fn triggering autocrine cytokine synthesis and release, thereby promoting their survival and persistence within the tissues.

Cell Survival↗
PubMed1994

Eosinophil adhesion to nasal polyp endothelium is P-selectin-dependent.

Tissue eosinophilia is a characteristic feature of a number of inflammatory diseases including asthma and nasal polyposis. Eosinophil migration into tissues is controlled in part by interactions between eosinophil adhesion receptors and counter-structures on the vascular endothelium. To determine the receptors used by eosinophils to adhere to vascular endothelium in allergic inflammation we have adapted the Stamper-Woodruff frozen section assay (FSA) to study eosinophil adhesion to nasal polyp endothelium. Immunohistology indicated that intercellular adhesion molecule 1 (ICAM-1), E-selectin and P-selectin were well expressed by nasal polyp endothelium, whereas expression of vascular cell adhesion molecule 1 (VCAM-1) was weak or absent. Unstimulated human peripheral blood eosinophils adhered specifically to nasal polyp endothelium. Adherence was temperature and divalent cation-dependent and saturable at cell densities > 5 x 10(6) cells/ml. Eosinophil adhesion was almost completely inhibited by a monoclonal antibody (mAb) against P-selectin and by a chimeric molecule consisting of the Fc portion of human IgG and the lectin binding domain of P-selectin, which binds to the P-selectin ligand on leucocytes. Anti-Mac-1 mAb partially inhibited eosinophil adhesion whereas mAb against E-selectin, L-selectin, ICAM-1, VCAM-1, very late activation antigen 4, and lymphocyte function-associated antigen 1 had no effect. P-selectin is stored in intracellular granules within the endothelial cell and in vitro is only transiently expressed. To determine if P-selectin was expressed on the membrane of the nasal polyp endothelium we compared P-selectin expression in normal skin and nasal polyps after acetone fixation, which permeabilizes cells, and paraformaldehyde, which only allows staining of membrane expressed receptors. In the skin, good expression was seen with acetone fixation but no expression was seen after paraformaldehyde treatment, whereas in nasal polyps, similar expression was observed with both fixatives. In addition immunofluorescence with confocal microscopy demonstrated lumenal staining of nasal polyp endothelium indicating that P-selectin was located on the surface of endothelial cells while in skin only an intracellular granular distribution was apparent. Lastly, whereas eosinophils bound consistently to nasal polyp endothelium, no binding was observed to blood vessels in normal skin further supporting the idea that eosinophils were binding to membrane expressed and not intracellular P-selectin. The importance of P-selectin in eosinophil adhesion to nasal polyp endothelium suggests that P-selectin antagonists may be effective at inhibiting eosinophil accumulation at sites of allergic inflammation.

Adult↗
PubMed1994

Eosinophil adhesion in allergic inflammation.

Eosinophil adhesion has been studied in some detail in recent years, and a number of interesting observations have emerged. As with other aspects of eosinophil biology, there appears to be a greater similarity with basophils than with neutrophils in their pattern of adhesion interactions. A number of important differences with respect to neutrophils have emerged, which could be exploited for the treatment of eosinophil-mediated disease, including the observations that eosinophil adhesion can be modulated by selective cytokines such as IL-5 and that eosinophils, unlike neutrophils, express VLA-4 and alpha 4/beta 7. There is also tantalizing evidence emerging that eosinophils interact differentially with the selectins, with differing degrees of affinity of binding and possibly different counterreceptors. The extent to which these observations will be useful in treating allergic disease remains to be seen.

Cell Adhesion↗
PubMed1994

Mechanisms of eosinophil and basophil migration.

Considerable progress has been made in our understanding of the molecular mechanisms involved in eosinophil and basophil migration into sites of allergic inflammation. It is clearly a staged process, each stage offering a level of control over the cell specificity and degree of migration. On the basis of current evidence, the various receptors and mediators involved are summarized in Table 4. Once in the tissues, eosinophils may persist for several days or weeks, surviving under the influence of locally generated cytokines, and this persistence may also partly explain the selective tissue accumulation of eosinophils and basophils. Understanding the molecular mechanisms involved in leukocyte migration may lead to the discovery of selective and effective antagonists to treat allergic disease by preventing cell migration. Results in a number of animal models already suggest that this approach may be successful. The development of drugs that can be tested in the clinic is awaited with much interest.

Animals↗
PubMed1994

Adhesion to fibronectin primes eosinophils via alpha 4 beta 1 (VLA-4).

Human peripheral blood eosinophils adhered specifically to microtitre plates coated with plasma fibronectin (Fn) in a dose- and time-dependent fashion. Adhesion was optimal at 60 min at a concentration of 100 micrograms/ml. Adherence to Fn was up-regulated by platelet-activating factor (PAF; optimum concentration of 10(-6) M) and was significantly inhibited by a polyclonal anti-Fn antibody (P < 0.05). The following evidence suggested that eosinophil adhesion to Fn was mediated by alpha 4 beta 1: (1) eosinophil adherence to Fn was not inhibited by an Arg-Gly-Asp-Ser (RGDS) synthetic peptide; (2) there was a dose-dependent adherence of eosinophils to microtitre plates coated with the 40,000 MW proteolytic fragment of Fn that contains the CS-1 alpha 4 beta 1 binding region, whereas adherence to the 120,000 MW chymotryptic fragment of Fn, which contains the RGD-dependent binding site, was weak and only observed at high concentrations (> 250 micrograms/ml); (3) significant inhibition of eosinophil adherence to Fn was achieved by monoclonal antibodies (mAb) against the alpha chain of VLA-4 but not by a mAb against CD45 or a mouse myeloma antibody as negative controls. After adhesion to Fn, eosinophils were investigated for their capacity to release leukotriene C4 in response to stimulation with a suboptimal concentration of calcium ionophore (2 x 10(-6) M). Significant enhancement of release was detected with Fn-coated plates but not with the control bovine serum albumin (BSA) (P < 0.01). Furthermore, this enhancement was significantly inhibited by the alpha 4 beta 1 mAb HP2/1 (P < 0.05) but not by an anti-CD45 mAb. From these studies we conclude that (1) alpha 4 beta 1 (VLA-4) integrin is a major receptor for Fn on human eosinophils and (2) adhesion to Fn may prime eosinophils for mediator release during allergic inflammation.

Antibodies↗
PubMed1993

Adhesion to fibronectin prolongs eosinophil survival.

We have investigated the effect of adhesion to fibronectin (Fn) on the survival of eosinophils in culture. Peripheral blood eosinophils from normal human donors were separated by immunomagnetic selection and cultured in RPMI on Fn- (100 micrograms/ml) coated microtiter plates for up to 96 h. Survival was measured by trypan blue exclusion. There was a significant enhancement of eosinophil survival with Fn as compared with both bovine serum albumin-coated and uncoated wells (p < 0.05-0.01). Fn-induced eosinophil survival was comparable to that obtained with exogenous interleukin 3 (IL-3) or granulocyte/macrophage colony-stimulating factor (GM-CSF) and was inhibitable by antibodies against Fn, very late antigen 4 (VLA-4), IL-3, and GM-CSF. Supernatants from Fn-, but not BSA-coated wells contained picogram amounts of IL-3 and GM-CSF, and eosinophils cultured on Fn for 24 h expressed mRNA for GM-CSF as determined by in situ hybridization. Therefore, Fn prolongs eosinophil survival in culture by triggering autocrine generation of cytokines by eosinophils. Since neutrophils lack VLA-4, this could provide a partial explanation for the preferential accumulation of eosinophils at sites of allergic inflammation, as well as the predominant tissue localization of eosinophils in healthy individuals.

Antibodies↗
PubMed1991

Human eosinophil, but not neutrophil, adherence to IL-1-stimulated human umbilical vascular endothelial cells is alpha 4 beta 1 (very late antigen-4) dependent.

Eosinophils, through their ability to generate an array of potent mediators, are thought to be the major effector cells in a number of conditions, including parasitic infection, asthma, and other allergic diseases. The mechanism(s) by which eosinophils, as opposed to neutrophils, accumulate at inflammatory sites is unknown. One possible mechanism would be an eosinophil-specific pathway of adhesion to vascular endothelium. In this study we have demonstrated that human eosinophils, but not neutrophils, constitutively express alpha 4 beta 1 (CD49d/CD29). Expression was not increased on low density eosinophils or normal density cells stimulated with platelet-activating factor. Eosinophils, but not neutrophils, specifically adhered to COS cells transfected with vascular adhesion molecule-1 in a alpha 4 beta 1-dependent manner. Eosinophil, but not neutrophil, adhesion to IL-1 stimulated human umbilical vascular endothelial cells was significantly inhibited by alpha 4 beta 1 mAb at both 5 h (p less than 0.05) and 20 h (p less than 0.001). Inhibition of both resting and platelet-activating factor-(10(-7) M) stimulated eosinophil adhesion was observed. We conclude that the alpha 4 beta 1/vascular adhesion molecule-1 adhesion pathway may be involved in specific eosinophil, as opposed to neutrophil, migration into sites of eosinophilic inflammation.

Antigens, CD↗
PubMed1991

Interleukin-5 enhances the in vitro adhesion of human eosinophils, but not neutrophils, in a leucocyte integrin (CD11/18)-dependent manner.

Interleukin (IL-5) was found to enhance the adhesion of eosinophils, but not neutrophils, to both microvascular and large vein endothelial cells in a dose-dependent manner. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) and platelet-activating factor (PAF) enhanced both eosinophil and neutrophil adhesion. Significant increases in eosinophil CR3 expression, but not LFA-1, were observed following pre-incubation with PAF, IL-3, IL-5 or GM-CSF. Neutrophil CR3 expression was increased significantly by pre-incubation with PAF or GM-CSF, but not IL-3 or IL-5. Enhanced adhesion to human microvascular endothelial cells (HMVEC) or human umbilical vein endothelial cells (HUVEC) was inhibited by (ranked in order of potency) anti-CR3 alpha = common beta-chain greater than LFA-1 alpha. Anti-p150,95 alpha had no measurable effect. Basal expression of eosinophil CR3 with monoclonal antibody inhibited IL-5-induced eosinophil hyperadherence to HUVEC in a manner almost identical to inhibition in the presence of excess anti-CR3. Thus, a conformational or affinity change in adhesion receptors following activation seems more important than a simple increase in numbers. No inhibition of unstimulated eosinophil adhesion to HMVEC or HUVEC by CD11/18 monoclonal antibody was observed. These findings demonstrate that IL-5 enhances eosinophil, but not neutrophil, adherence reactions, by a mechanism dependent, at least in part, on the CD11/18 family of adhesion glycoproteins.

Antigens, CD↗
PubMed1991

Effects of cetirizine on human eosinophil and neutrophil activation in vitro.

The ability of cetirizine, a novel antihistamine agent, to inhibit the in vivo activation of human eosinophils, neutrophils and monocytes has been investigated using C3b- and IgG-dependent rosette formation, cytotoxicity against opsonised parasitic larvae and adherence to plasma-coated glass (PCG). The drug inhibited platelet-activating factor (PAF)-induced enhancement of eosinophil and neutrophil IgG (Fc) and complement (C3b) rosettes with an IC50 of 2 x 10(-5) M. There was also comparable inhibition of PAF-dependent enhancement of eosinophil cytotoxicity (for complement-coated schistosomula of Schistosoma mansoni). Cetirizine inhibited PAF-induced eosinophil, but not neutrophil, hyperadherence to PCG. These data support the view that cetirizine may exert some of its anti-allergic effects by inhibiting the activation of human granulocytes and that it may also selectively inhibit PAF-induced eosinophil hyperadherence.

Animals↗
PubMed1990

Receptor expression and functional status of cultured human eosinophils derived from umbilical cord blood mononuclear cells.

Selective use of recombinant human cytokines has enabled the culture of large numbers of eosinophils from human cord blood mononuclear cells, raising the possibility of their use as a model of eosinophil function. Cultured eosinophils (CE) were compared with normal-density peripheral blood eosinophils (PBE) in terms of their membrane receptor expression and function. Fc gamma R and CR1 expression of CE and PBE was similar. In contrast, the specific mean fluorescence for LFA-1 alpha, p150,95 alpha, ICAM-1, and HLA-DR was significantly elevated for CE compared with PBE. CE responded in PAF-induced chemotaxis in a similar fashion to PBE. CE gave higher numbers of both resting and platelet activating factor (PAF)-stimulated immunoglobulin G (IgG)- and C3b-dependent rosettes than PBE. CE and PBE had comparable capacity to kill IgG- and C-opsonized schistosomula in terms of both baseline values and PAF-induced enhancement of cytotoxicity. Baseline adherence by CE and PBE to plasma-coated glass was essentially the same, but stimulated adhesion (PAF) of CE was lower. Compared with PBE, CE generated less than half the amounts of extracellular and cell-associated PAF induced by calcium ionophore A23187 stimulation. Unlike PBE, CE did not generate PAF after exposure to IgG-coated Sepharose particles. CE stimulated with IgG-coated beads generated small quantities of LTC4, while A23187 stimulation resulted in approximately half the LTC4 levels observed with PBE. The total cell content of eosinophil peroxidase (EPO) was similar for CE and PBE. These data suggest that although CE and PBE have many phenotypic and functional properties in common there are quantitative differences that may be a consequence of their immaturity and/or the influence of the cytokines used in their culture.

Animals↗
PubMed1990

Enhancement of the expression of eosinophil IgE receptor (Fc epsilon R2) and its function by platelet-activating factor.

Eosinophils possess low-affinity Fc immunoglobulin E (IgE) receptors (Fc epsilon R2). We have compared platelet-activating factor (PAF) with lyso-PAF, leukotriene B4 (LTB4) and histamine for their ability to influence the binding of a native myeloma IgE to normal-density human eosinophils, using flow cytometry and a fluorescein-conjugated anti-IgE polyclonal antibody. Preincubation with PAF gave a dose- and time-dependent increase in IgE binding optimal at 10(-7) M (P less than 0.01) and 30 min respectively. A smaller but significant effect was observed with LTB4 and histamine (optimal at 10(-7) M (P less than 0.01) and 10(-5) M (P less than 0.05) respectively). Diluent alone or lyso-PAF had no effect. These results suggest enhanced expression of Fc epsilon R2 by stimulated eosinophils. Further confirmation of enhancement was obtained using two functional assays, i.e., cytotoxicity and mediator (LTC4) generation. IgE-dependent cytotoxicity against schistosomula of Schistosoma mansoni was enhanced by prior incubation of normal eosinophils with PAF (optimal at 10(-7) M), but not lyso-PAF. No LTC4 was detectable following incubation of unstimulated eosinophils with S. mansoni coated with specific IgE. Preincubation of these cells with PAF (10(-7) M) resulted in the generation of 4.4 pmol of LTC4 per 10(6) cells. Our data demonstrate that normal-density eosinophil Fc epsilon R2 expression can be up-regulated in vitro by PAF and LTB4 and that these changes are accompanied by enhanced functional properties.

Animals↗
PubMed1990

Fc gamma and CD11/CD18 receptor expression on normal density and low density human eosinophils.

We have studied the expression of Fc gamma receptors and leucocyte integrins (CD11/CD18 family) on human eosinophils using specific monoclonal antibodies (mAb) and flow cytometric analysis. Peripheral blood eosinophils of normal density and low density were compared with neutrophils and monocytes. Several properties of the human eosinophil were established. These were (i) that the eosinophil expressed Fc gamma RII (CDw32) only (unlike monocytes which bear Fc gamma RI and Fc gamma RII and neutrophils which bear Fc gamma RII and Fc gamma RIII); (ii) that the absence of Fc gamma RIII (CD16) on eosinophils served as a basis for distinguishing eosinophil and neutrophil populations by immunofluorescence; (iii) that the leucocyte adhesion glycoproteins, LFA-1 alpha (CD11a), CR3-alpha (CD11b), p150, 95-alpha (CD11c) and the common beta-chain (CD18), were expressed on the eosinophil as well as the neutrophil; (iv) that CD18 expression was significantly reduced on low-density eosinophils from the hypereosinophilic syndrome. Thus, our findings emphasize the unique phenotype of the human eosinophil in terms of Fc gamma receptor expression, the similarity of the eosinophil and neutrophil with regard to the leucocyte integrins and that eosinophils of low density do not differ greatly from those of normal density in terms of receptor expression.

Antigens, Differentiation↗
PubMed1990

IL-5 enhances the in vitro adhesion of human eosinophils, but not neutrophils, in a leucocyte integrin (CD11/18)-dependent manner.

In an attempt to explain the preferential accumulation of eosinophils at sites of allergic tissue reactions, we have studied the effects of interleukin-5 (IL-5) on the adherence of human eosinophils and neutrophils to plasma-coated glass (PCG) or human microvascular endothelial cells (HMVEC). IL-5 was compared with IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and platelet-activating factor (PAF), since all these agents have biological properties associated with eosinophil activation and/or survival in vitro. IL-5, IL-3 and GM-CSF induced a time-dependent increase in adherence of normal density eosinophils to PCG optimal at 60 min, whereas the effect of PAF was greater at 15 min. Similar results were obtained with neutrophils, with the exception that IL-5 had minimal and non-significant effects on this cell type. Unstimulated eosinophils and neutrophils also adhered to PCG or HMVEC, but in low numbers. Preincubation of eosinophils with IL-5, GM-CSF or PAF resulted in dose-dependent increases in the numbers of adherent cells to PCG. IL-3 had a smaller but significant effect on enhanced eosinophil adhesion to PCG, while IL-2 and lyso-PAF were ineffective. Neutrophils gave similar levels of baseline and stimulated adhesion to PCG as eosinophils, IL-5 again had no significant stimulatory effect. IL-5 also increased eosinophil, but not neutrophil, adherence to HMVEC in a concentration-dependent manner. Preincubation with the protein synthesis inhibitor cycloheximide had no effect on IL-5-, GM-CSF- or PAF-stimulated eosinophil adhesion. The contribution of the CD11/18 leucocyte integrins to IL-5- and PAF-induced eosinophil hyperadherence was investigated by inhibition experiments utilizing monoclonal antibodies (mAb). Enhanced adhesion to PCG (by PAF) or HMVEC (by IL-5) was inhibited by (ranked in order of potency) anti-CR3 alpha = common beta-chain greater than LFA-1 alpha. Anti-p150,95 alpha had no measurable effect. Baseline adhesion by unstimulated eosinophils was not significantly influenced by prior incubation with these mAb. Using flow cytometry, IL-5 and IL-3 were found to up-regulate cosinophil but not neutrophil CR3 expression. These findings demonstrate that IL-5 enhances cosinophil, but not neutrophil, adherence reactions, by a mechanism dependent, at least in part, on the CD11/18 family of adhesion glycoproteins.

Cell Adhesion↗
PubMed1990

The effect of platelet-activating factor on IgE binding to, and IgE-dependent biological properties of, human eosinophils.

This study investigated the effect of platelet-activating factor (PAF), leukotriene B4 (LTB4) histamine and formyl-methionyl-leucyl-phenylalanine (FMLP) on immunoglobulin E (IgE) binding and IgE-dependent cytotoxicity of human normal density eosinophils. The binding of a native myeloma IgE to normal human eosinophils was measured by flow cytometry using a fluorescein-conjugated polyclonal anti-IgE antibody. Preincubation with PAF (optimal at 10(-7)M), but not lyso-PAF or FMLP, gave dose-dependent increases in IgE binding. PAF and LTB4 gave significant increases in IgE binding after 5 min preincubation (P less than 0.05); the effect was further enhanced at 30 min (P less than 0.01). This was further confirmed using the rosette assay where PAF and LTB4, but not lyso-PAF or FMLP, gave dose- and time-dependent increases in IgE eosinophil rosettes. Eosinophil cytotoxicity for schistosomula of Schistosoma mansoni, incubated with immune serum, was also significantly enhanced (P less than 0.01) by PAF in a dose-dependent fashion (optimal at 10(-8) M). Schistosomula coated with FPLC-purified IgE fractions were susceptible to killing by normal density eosinophils, and this was enhanced with PAF (10(-8)M), LTB4 (10(-7)M) and histamine (10(-5)M) but not with FMLP (10(-7)M) or lyso-PAF. IgE-dependent cytotoxicity was confirmed by the removal of contaminating IgG from IgE-rich fractions, and by the abolishment of IgE-dependent cytotoxicity after IgE adsorption. These results suggest that PAF (and to a lesser extent LTB4 and histamine) increase IgE binding, IgE-dependent adherence and cytotoxicity of normal human eosinophils. Although IgE receptors have not been identified, the data support current concepts that certain biological properties of eosinophils may be IgE associated.

Cells, Cultured↗
PubMed1989

A case of exercise-induced anaphylaxis: evidence of an association with the complement system.

We studied a 17-year-old girl with exercise-induced anaphylaxis (EIA). She experienced 10 episodes of EIA which demonstrated cutaneous, digestive and cardiorespiratory symptoms. This subject exhibited elevation in plasma histamine (13.3 ng/ml) and decrease in CH50 (17 U/ml) and C3 (70 mg/dl) after naturally induced EIA. On remission day CH50 (26 U/ml), C3 (83 mg/dl) and C4 (15 mg/dl) were of relatively low values. Her mother demonstrated the same tendency with a low level of C4 (14 mg/dl), and this suggested an underlying genetic disorder in the complement system. Exercise challenge could not elicit EIA symptomatically but showed fluctuation of CH50. The triggering mechanism of EIA was unclear; however there is a possibility that complement plays an important role in EIA.

Adolescent↗