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PubMed1979

Metabolic studies on the uptake of [14C]-histidine and [14C]-histamine and histamine synthesis by guinea-pig basophils, in vitro.

The uptake of [14C]-histidine and [14C]-histamine and the conversion of [14C]-histidine to [14C]-histamine was measured in suspensions of guinea-pig bone marrow cells rich in basophils. When comparable amounts of labelled histidine or histamine were added to equal numbers of basophils, the uptake of histidine was approximately forty-five times greater than that of histamine. Purified eosinophils, neutrophils and mononuclear cells incorporated only a small proportion of [14C]-histidine when compared to the basophil; [14C]-histamine uptake by all these cell types was virtually negligible. Histidine uptake and the amount of histamine formed de novo was directly related to the number of basophils, the time of incubation and the substrate concentration. Histidine uptake was decreased by agents which inhibit glycolysis, oxidative phosphorylation, Na + - K + -dependent ATPase, protein synthesis and RNA synthesis. Inhibition was demonstrable in a dose-dependent fashion and at concentrations which had no apparent effect on cell viability. Inhibitors of DNA synthesis, and of microtubule function, had no influence on histidine uptake. Cytochalasin B, an inhibitor of microfilament function, also decreased histidine uptake but only at concentrations previously showen to affect hexose transport. None of the agents tested affected the uptake of [14C]-histamine or the amounts of new histamine formed from the histidine that had been incorporated. These studies suggest that histidine is preferentially incorporated into the basophil; that the uptake depends on the integrity of a number of metabolic pathways, but that once the histidine is taken up these requirements do not apply to the formation of new histamine. In contrast, histamine appeared to diffuse passively, and in relatively small amounts, into all the cell types tested.

Animals↗
PubMed1983

The interaction of human and rodent IgE with the human basophil IgE receptor.

The cross-reactivity of the human IgE receptor with mouse and rat IgE was studied. Using leukocytes from a patient with chronic myelogenous leukemia, in which the mononuclear fraction contained up to 75% basophils, both rat and mouse IgE were found to inhibit the binding of 125I-human IgE to the human basophilic leukemia (HBL cells). About 15-fold more rodent IgE was required for 50% inhibition of binding than unlabeled human IgE (hIgE). Dose-response studies using increasing amounts of rodent vs human 125I-IgE indicated that the HBL cells had about 8000 receptors per cell for hIgE and 5500 receptors per cell for rodent IgE. When the HBL cells were surface labeled with 125I and subsequently solubilized with non-ionic detergent, the labeled hIgE receptor could be isolated by either affinity chromatography on IgE-Sepharose (either human or rodent) or by immunoprecipitation with hIgE and anti-IgE. By SDS-PAGE on 10% gels, the receptor had a m.w. of 58,000 daltons. The solubilized receptors exhibited some rebinding to hIgE-Sepharose, and this rebinding could be inhibited by either human or rodent IgE but not by human IgG. Both the HBL cells and normal human basophils could be passively sensitized with murine IgE anti-DNP for antigen-induced histamine release. The minimum concentration of the mouse IgE antibody for sensitizing normal basophils was 20 to 200 ng/ml. Pretreatment of basophils with human IgE, but not human IgG, abrogated the capacity of the murine IgE antibody to sensitize the cells for histamine release, which indicated that the human and rodent IgE were interacting with the same receptor.

Animals↗
PubMed1984

Stimulation of basophil and rat mast cell histamine release by eosinophil granule-derived cationic proteins.

Major basic protein (MBP), an arginine-rich basic polypeptide that constitutes the crystalloid core of the large specific eosinophil granule, has previously been shown to stimulate noncytolytic histamine release from human basophils and rat mast cells by an IgE-independent mechanism. Two additional basic polypeptides present in eosinophil granules, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), were examined for similar activity in the present study. Acid-solubilized eosinophil granules were fractionated by chromatography on a Sephadex G-50 column. Incubation of basophil-containing human mononuclear cells with the individual column fractions demonstrated that histamine release occurred only with the fractions that contained MBP. The selectivity of the basophil response for MBP was confirmed by using equimolar concentrations of purified MBP, ECP, and EDN. In contrast, both MBP and ECP, but not EDN, stimulated histamine release from purified rat peritoneal mast cells. Reduction and alkylation of the MBP molecule diminished the response of human basophils to MBP but enhanced the potency of the molecule with rat mast cells. The distinct potency of MBP as a stimulus for histamine secretion from human basophils suggests that eosinophil release of MBP may be a specific event in the augmentation of immediate hypersensitivity reactions and other disorders characterized by eosinophilia.

Animals↗
PubMed1984

An in vitro study of basophil production in chronic myeloproliferative disorders.

An examination was carried out of certain parameters of basophil production in semisolid agar cultures by granulomonocyte precursors (CFU-C) from normal subjects and from patients with chronic myeloproliferative disorders. Basophils were rare in the first four days of culture, after which their number increased gradually to reach a plateau on about the 12th day. Pure basophil colonies were frequent only in cultures from a patient with marked basophilia. In the other cases the colonies also included other cells of the granulomonocyte pathway. There was a linear correlation between basophilia in vivo and basophil production in vitro. The latter, however, was influenced by the type of colony-stimulating activity (CSA) used. Different CSA sources, inducing the production of a comparable number of colonies, did not stimulate basophilic differentiation in the same way. Serum from patients with chronic myelocytic leukemia and varying degrees of basophilia did not have a significant effect on autologous in vitro basophilopoiesis, nor did it increase that of normal CFU-C.

Basophils↗
PubMed1983

Purified human basophils and mast cells: current concepts of mediator release.

Mediators released from human basophils and mast cells in response to immunologic and other stimuli are felt to be important in the pathophysiology of several nasal and pulmonary disease processes. Recently, we have developed techniques to purify these cells, thus allowing precise ultrastructural, biochemical and pharmacological studies of mediator release. Previous literature has emphasized the similarities of the two cell types including their metachromatic staining and IgE-mediated release of mediators. However, we now appreciate that several differences exist between the two cell types. At the ultrastructural level, basophil release is characterized by individual granules emptying to the cell exterior, while mast cell granules fuse intracellularly and release their contents through cytoplasmic channels. Functionally, basophils are 10- to 30-fold more sensitive than mast cells to anti-IgE, but the kinetics of release are less rapid. Basophil, but not mast cell, release is (I) inhibited by histamine H2 agonists and glucocorticoids; (II) enhanced by PgD2 and (III) modulated by arachidonic acid lipoxygenase metabolites. Significant quantities of slow-reacting substance of anaphylaxis, PgD2 and platelet-activating factor are generated by mast cells. Basophils produce little or none of these mediators. Studies with these purified, relevant human cell types should provide important insights into the cellular basis of hypersensitivity states and their control.

Basophils↗
PubMed1983

IgE antibody-mediated cutaneous basophil hypersensitivity reactions in guinea pigs.

Cutaneous basophil hypersensitivity (CBH) reactions are a heterogeneous group of delayed time course basophil-rich immune responses that can be mediated in the guinea pig by T cells, B cells, or IgG1 antibody. This study examined whether guinea pig IgE antibody could also mediate CBH reactions. IgE antibody to picryl or oxazolone determinants was induced by immunizing Hartley strain guinea pigs pretreated with cyclophosphamide. Hyperimmune serum from these animals was passed through a heavy chain-specific anti-IgG1 affinity column. The presence of IgE anti-hapten antibody in the filtrate fraction was verified by passive cutaneous anaphylaxis (PCA) testing with a 7-day period of local passive sensitization and by the heat lability (56 degrees C, 4 hr) of PCA activity. This IgE-rich fraction and the IgG1 fraction eluted from the column with base (0.2 M Na2CO3, pH 11.3) were transferred i.v. to separate groups of normal guinea pigs. Both fractions mediated delayed time course reactions that contained basophils. Macroscopic and microscopic reactions mediated by the IgE-rich fraction were abolished with heat (56 degrees C, 4 hr). Thus, two antigen-specific factors in guinea pig serum can mediate delayed time course basophil-containing reactions: IgG1 and IgE antibodies. IgE-mediated CBH reactions are similar to the late-phase reaction that follows IgE-dependent wheal-and-flare reactions in humans. The finding that guinea pig IgE can mediate a late reaction that contains basophils makes this a possible model for the human late-phase response, and suggests that some forms of CBH may play a role in human allergic disease.

Animals↗
PubMedDate not supplied

Follow-up of sixty two cases of acute basophilic leukemia.

62 cases of ABL have been investigated over the last 20 years. In our series ABL were 5% of all acute leukaemias. Four ABL types can be distinguished : (a) the basophilic terminal phase (basophilic blastic crisis) of cronic myeloid leukemia; (b) the mixed basophilic-oesinophilic types; (c) the promyelocytic basophilic type; and (d) histio basoblastic type. The first two are quite rare. The promyelocytic basophilic type can be easily differentiated from PNL; the frequency of the latter is three times higher. Fundamental to diagnosis are cytochemical stains specific for acid mucopolysacchaes. Myelobiopsy is always essential since in almost 50% of the cases no typical cells appears in the peripheral blood. In the bone marrow Ab are very numerous and and pleiomorphic. ABL is marked from its onset by a severe symptomatology. In contrast to our experience in PNL, only do some patients with ABL achieve complete remission.

Basophils↗
PubMed1977

Systemic expression of cutaneous basophil hypersensitivity.

Guinea pigs primed for cutaneous basophil hypersensitivity (CBH) with several soluble proteins or with sheep erythrocytes developed a systemic, delayed-onset, maculopapular rash when challenged parenterally with specific antigen. The rash was most readily induced 5 to 7 days after immunization, at a time when local CBH skin test reactivity was also optimal. Miscroscopically, the rash resembled local CBH skin test reactions, being comprised of a papillary dermal infiltrate of basophils and lymphocytes and a striking dilatation and compaction of superficial venules. In addition to the systemic rash, animals expressing systemic CBH (SCBH) exhibited a striking eosinophilia at 24 hr which gave way to basophilia at 48 hr. Focal collections of eosinophils, and of smaller numbers of basophils, were found in the lungs and spleen; both eosinophils and basophils infiltrated the medulla of the thymus. Thus, basophil-rich infiltrations are favored in the skin even after systemic challenge with antigen and occur only to a much smaller extent in other organs where eosinophils may predominate. These differences in the response of various organs to challenge with parenteral antigen suggest that as yet unidentified local factors play a determinative role in regulating the inflammatory response. The pathogenesis of SCBH is not yet established, but it shares many of the properties of local CBH: histology, carrier specificity, development early after sensitization in the absence of detectable antibodies. Passive transfer has not been accomplished with serum alone but has been achieved irregularly with cells plus serum. SCBH may serve as a useful model for several disease states in man characterized by a systemic rash and eosinophilia, including certain types of drug reaction.

Animals↗
PubMedDate not supplied

Evidence for the involvement of the IgE-basophil-mastocyte system in human acute post-streptococcal glomerulonephritis.

Several findings reveal the involvement of the IgE-basophil-mastocyte-platelet-activating-factor (PAF) system in human acute post-streptococcal glomerulonephritis. In the acute phases of the disease there is a transient, marked reduction in the circulating metachromatically staining basophils, indicating an in vivo basophil degranulation. The blood reservoirs of PAF are depleted. The number of metachromatic mastocytes in renal biopsy samples was very low and morphological aspects of degranulation were present. In vitro, we demonstrated basophil degranulation and PAF release in presence of exogenous streptococcal Ags after recovery. These findings suggest that the IgE-basophil-mastocyte-PAF system may play a role in human pathology, as has been shown in immune complex (Ic) deposition in acute serum sickness in rabbits.

Acute Disease↗
PubMed1981

Cutaneous basophil responses and immune resistance of guinea pigs to ticks: passive transfer with peritoneal exudate cells or serum.

Resistance to infestation by larval Amblyomma americanum or Rhipicephalus sanguineus ticks was transferred to naive guinea pigs with peritoneal exudate cells (PEC) or serum from donors immunized by prior infestation with homologous tick larvae. In the A. americanum system, PEC transfer induced 87% tick rejection, which was similar to the level of resistance in actively sensitized hosts. In the R. sanguineus system, PEC conferred resistance (39% rejection) that was weaker than in actively sensitized hosts (57% rejection). In both systems, immune serum conferred significant but weaker resistance (20 to 29% rejection). In actively sensitized hosts, resistance to each tick species was specific, but there was considerable cross-reactive resistance. Basophils dominated the 24-hr challenge feeding sites of A. americanum ticks in actively sensitized hosts (69% of the infiltrate) and recipients of sensitized PEC (69%). Mononuclear cells were dominant (69% of the infiltrate) in the challenged tissues of immune serum recipients that had a significant but weaker cutaneous basophil response (24%). Mononuclear cells also dominated (58% of the infiltrate) the 24-hr challenge feeding sites of R. sanguineus ticks in actively sensitized hosts, but there were also 24% basophils. These studies demonstrate that immune resistance to tick is dependent on sensitized lymphoid cells or serum components, and that sensitized cells or serum can transfer a cutaneous basophil response that is associated with immune resistance. Rejection of ticks is usually associated with large basophil infiltrates, but sometimes mononuclear cells are dominant. Thus, immune resistance of guinea pigs to ticks is a heterogeneous response in which immune cells and serum probably act to recruit diverse effector leukocytes to mediate rejection that is specific but significantly cross-reactive.

Animals↗
PubMed1995

The antineoplastic bryostatins affect human basophils and mast cells differently.

Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multi-potential stimulators of immune cells. We have examined the effects of bryostatins on mediator release from human basophilic leukocytes and human tissue mast cells. Bryostatins 1, 2, and 5 (10 to 3,000 nmol/L) induced histamine secretion from purified and unpurified peripheral blood basophils, whereas they caused no release of peptide-leukotriene C4 from these cells. The rate of histamine release caused by bryostatin 1 was slower than that caused by anti-IgE (t1/2 +/- SEM = 38.2 +/- 4.7 minutes v 8.9 +/- 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37 degrees C, approximately 30% less at 30 degrees C, and no release at 22 degrees C or 4 degrees C). The addition of increasing concentrations of extracellular Ca2+ to the medium caused histamine release in the presence of bryostatins. Subeffective concentrations of bryostatins and anti-IgE produced a synergistic effect on histamine release from basophils. Staurosporine, chelerythrine, and calphostin C (0.1 to 10 nmol/L), which are protein kinase C inhibitors, inhibited the histamine secretion activated by bryostatin 1 and tetradecanoylphorbol-acetate (TPA). Preincubation with granulocyte-monocyte colony-stimulating factor (GM-CSF; 1 and 5 nmol/L) and interleukin-3 (IL-3; 10 ng/mL) potentiated the activation of human basophils induced by bryostatin 1. Neither bryostatin 1 nor bryostatin 2 induced the release of histamine from mast cells isolated from human lung or skin tissues. However, brief (10 minutes) preincubation with bryostatin 1 (3 to 300 nmol/L) potently inhibited the histamine secretion induced by anti-IgE from skin or lung mast cells. Bryostatin 1 was a more potent (by approximately 30 times) inhibitor of IgE-mediated histamine release than was TPA. The heterogeneous effects exerted by bryostatins on human basophils and mast cells can be of interest for those designing therapeutic trials using these agents.

Antibodies, Anti-Idiotypic↗
PubMed1993

Modulation of human basophil histamine release by insulin-like growth factors.

Several lines of evidence indicate that basophils play an active pathogenic role in the late-phase reaction. Inasmuch as various cytokines are produced locally by activated cells of the immune system during late-phase reaction, "priming" of basophils by cytokines has become an area of active study over the last few years. We studied the effect of insulin-like growth factor (IGF)-I, shown to be active on immature and mature hemopoietic cells, on histamine release from human basophils. IGF-I enhanced histamine release initiated by anti-IgE, calcium ionophore A23187, and phorbol ester in a dose-dependent fashion (ED50: 300-600 pM), although IGF-I had little or no effect on the release caused by FMLP and C5a. The priming effect of IGF-I took place rapidly and reached plateau levels in 15 min. IGF-II and insulin, both of which have high amino acid sequence homology with IGF-I, also primed basophils. The order of enhancing potencies was IGF-I > IGF-II > insulin; IGF-I was 10-fold more potent than IGF-II and 250-fold more potent than insulin. Although specific receptors for each factor have been identified, blocking experiments using a mAb against IGF-I receptor showed almost complete abolishment of the enhancing effect of these factors, indicating that the enhancing effect is exhibited via the IGF-I receptor. Inasmuch as IGF-I has been shown to be produced by alveolar macrophages, fibroblasts, and nasal polyps, these results indicate that IGF may regulate allergic reactions in vivo by enhancing histamine release from basophils.

Basophils↗
PubMed1993

Characterization of the human basophil response to cytokines, growth factors, and histamine releasing factors of the intercrine/chemokine family.

We have tested the histamine releasing properties and priming abilities of a wide range of recombinant or purified cytokines and growth factors on the basophils of 20 subjects (10 atopic and 10 nonatopic). We found that monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), RANTES, human macrophage inflammatory protein-1 alpha and human inflammatory protein-1 beta, Connective tissue activating peptide III and Neutrophil Activating Peptide-2 (NAP-2) cause histamine release from basophils and are all members of the intercrine/chemokine family. MCAF/MCP-1 was as potent as anti-IgE or C5a and it is clearly the major contributor to histamine releasing factor activity. RANTES was the second major histamine releasing factor among the positive cytokines. Both MCAF/MCP-1 and RANTES are present in conditioned mononuclear cell media and can be separated using Mono Q anion exchange chromatography. We also demonstrated that RANTES has unusual chromatographic properties in spite of its isoelectric point of > 9.0 because it is largely found in peak-2 of the Mono Q column rather than peak-1 in which intercrines such as MCAF/MCP-1, IL-8, and connective tissue activating peptide III are found. All other cytokines and growth factors tested were negative, with the exception of IL-3, which caused histamine release in a subpopulation of subjects, and also primed basophils for release by anti-IgE. Other basophil primers for anti-IgE-dependent histamine release were IL-5, mast cell growth factor (c-kit ligand), and insulin-like growth factor II. Using specific neutralizing antibodies we have shown that MCAF/MCP-1, RANTES, and IL-3 contribute significantly to the activity found in mononuclear cell culture supernatants. Granulocyte-macrophage-CSF, IP-10, I-309, IL-7, IL-8, IL-9, IL-10, IL-11, IgE-binding factor, TNF-alpha, TGF-beta 1, fibroblast growth factor, epidermal growth factor, and endothelial cell growth factor were negative for direct histamine release and as primers of basophils. Our results indicate that cytokines belonging to the intercrine/chemokine family are major constituents of the activity known as "histamine releasing factor" found in MNC supernatants.

Animals↗
PubMed1993

Protein Fv produced during vital hepatitis is a novel activator of human basophils and mast cells.

Protein Fv is found in the normal liver and is released in the stools of patients suffering from viral hepatitis. Protein Fv isolated from five patients stimulated the release of histamine and sulfidopeptide leukotriene C4 from purified and unpurified peripheral blood basophils. Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion, whereas removal of putative contaminating Ig did not modify the releasing activity. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE). There was an excellent correlation (Spearman rank coefficient (rs) = 0.83; p < 0.001) between the maximal percent histamine release induced by protein Fv and that induced by anti-IgE from basophils. Preincubation of basophils with either protein Fv or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with heterologous stimulus. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released histamine in response to anti-IgE and protein Fv. A monoclonal IgE purified from a myeloma patient (patient ADZ) blocked both anti-IgE- and protein Fv-induced releases, whereas human polyclonal IgG and a monoclonal IgG purified from another myeloma patient (patient ZEG) selectively blocked protein Fv-induced secretion. Protein Fv also induced the release of preformed (histamine and tryptase) and de novo synthesized mediators (sulfidopeptide leukotriene C4 and/or PGD2) from mast cells purified from human lung parenchyma and skin tissues. There was a significant correlation between the maximal percent histamine release induced by protein Fv and anti-IgE from skin mast cells (rs = 0.63; p < 0.01). There was also an excellent correlation between histamine and tryptase release caused by protein Fv from both lung (rs = 0.80; p < 0.001) and skin mast cells (rs = 0.70; p < 0.01). Thus, we established that protein Fv acts as a novel activator of human basophils and mast cells presumably by interacting with the VH domain of the IgE.

Animals↗
PubMed1994

[Human basophilic granulocytes and mast cells: mediators between allergic inflammation and the specific immune system].

Basophils and mast cells represent important effector cells in allergic inflammation. Furthermore, these cell types are suggested to play a role in the pathogenesis of other forms of chronic inflammation and in the maintenance of tissue homeostasis. Recent studies provided new information on the morphology, development, distribution and effector function of the histamine-containing cells. Particularly the identification of new surface membrane molecules such as CD40 ligand on basophils or c-kit on mast cells, and of new triggering agents and modulators of mediator release such as IL-3, IL-5, GM-CSF and nerve growth factor (for basophils) or c-kit ligand (for mast cells) allows a better understanding of the regulation of these cell types. The regulating cytokines are produced by lymphocytes and tissue cells. On the same time, membrane proteins and soluble mediators of basophils and mast cells regulate tissue and immune functions. Thus, basophils and mast cells are not only effectors but also regulators of inflammation. It is, therefore, tempting to speculate that both cell types play an important role as mediator cells between the unspecific effector level and the specific antigen-recognizing cells of the host immune defense system. This review is mostly restricted to the human system.

Basophils↗
PubMed1993

Ultrastructural characteristics of Fc epsilon R-positive basophils in the spleen and bone marrow of mice immunized with goat anti-mouse IgD antibody.

BACKGROUND: Previous work showed that injection of mice with goat anti-mouse IgD antibodies results in increased numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen and Fc epsilon R-positive cells in the bone marrow, and that some of these cells had ultrastructural features of basophils. Fc epsilon R-positive, non-B, non-T cells express virtually all of the capacity of mouse splenic "non-B, non-T cells" to produce interleukin-4 in response to stimulation by cross-linking of Fc epsilon R or Fc gamma R, or by the calcium ionophore, ionomycin. EXPERIMENTAL DESIGN: The present study is a detailed ultrastructural analysis of Fc epsilon R-positive bone marrow cells or Fc epsilon R-positive splenic non-B, non-T cells sorted from mice injected with goat anti-mouse IgD antibody and of Fc epsilon R-positive bone marrow cells or spleen cells pooled from normal mice not injected with goat anti-IgD. RESULTS: Basophils represented the majority (90%) of the granulated cells present in the Fc epsilon R-positive splenic non-B, non-T cells or Fc epsilon R-positive bone marrow cells of goat anti-IgD-injected mice. In contrast, the cytoplasmic granule-containing Fc epsilon R-negative cells sorted from spleen or bone marrow of goat anti-IgD-injected animals contained predominantly a mixture of neutrophils, eosinophils, monocytes and their precursors. Both the Fc epsilon R-positive and -negative preparations contained rare (< 5%) cells with ultrastructural features of very immature mast cells. Basophils were also identified in Fc epsilon R-positive cells sorted from total bone marrow cells or spleen cells of normal mice not injected with goat anti-IgD. CONCLUSIONS: Taken together with data concerning the numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen, and Fc epsilon R-positive B220-negative cells in the bone marrow, these ultrastructural findings indicate that injection of mice with goat anti-IgD results in increased numbers of basophils, particularly in the spleen, that exhibit an 8-fold increase in basophils as a result of injection of goat anti-IgD.

Animals↗
PubMed1997

Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody.

Treatment of allergic disease by decreasing circulating IgE with anti-IgE Abs is currently under clinical study. Based on previous unrelated studies, it appeared likely that Fc(epsilon)RI expression on basophils and mast cells might also be regulated by levels of circulating IgE Ab. Therefore, the expression of IgE and Fc(epsilon)RI on human basophils was examined in 15 subjects receiving humanized anti-IgE mAb intravenously. Treatment with the anti-IgE mAb decreased free IgE levels to 1% of pretreatment levels and also resulted in a marked down-regulation of Fc(epsilon)RI on basophils. Median pretreatment densities of Fc(epsilon)RI were approximately 220,000 receptors per basophil and after 3 mo of treatment, the densities had decreased to a median of 8,300 receptors per basophil. Flow cytometric studies, conducted in parallel, showed similar results and also showed in a subset of 3 donors that receptors decreased with a t1/2 of approximately 3 days. The responsiveness of the cells to IgE-mediated stimulation using anti-IgE Ab was marginally decreased (approximately 40%) while the response of the same cells to stimulation with dust mite Ag, Dermatophagoides farinae, was reduced by approximately 90%. One possible explanation for these results is that Fc(epsilon)RI density is directly or indirectly regulated by plasma-free IgE levels.

Adult↗
PubMed1997

Recombinant histamine-releasing factor enhances IgE-dependent IL-4 and IL-13 secretion by human basophils.

Human recombinant histamine-releasing factor (HrHRF) is known to directly stimulate histamine release and IL-4 secretion from basophils of selected atopic donors in a reaction requiring the expression of a particular type of IgE, referred to as IgE+. In this study, HrHRF is shown to affect the IgE-mediated release of IL-4, IL-13, and histamine from basophils not normally releasing to this protein (i.e, those expressing IgE-). Priming with several different concentrations of HrHRF for 15 min enhanced basophil secretion of IL-4 and histamine after 4 h in a dose-dependent fashion following activation with anti-IgE Ab (10 ng/ml). This effect of HrHRF priming also occurred in cultures activated with 1 or 100 ng/ml of anti-IgE Ab. The secretion of IL-13 protein was enhanced similarly by HrHRF priming in cultures stimulated for 16 to 20 h with anti-IgE Ab. There were, however, no apparent changes in the secretion of histamine or cytokine by basophils primed with HrHRF and activated with the IgE-independent secretogogue, FMLP. These findings suggest that HrHRF modifies the response of basophils for IgE-dependent secretion by binding to a specific receptor, broadening the possible role of this protein in chronic allergic inflammation.

Basophils↗