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PubMed2006

Stimulation of human endothelium with IL-3 induces selective basophil accumulation in vitro.

Basophils have been shown to accumulate in allergic airways and other extravascular sites. Mechanisms responsible for the selective recruitment of basophils from the blood into tissue sites remain poorly characterized. In this study, we characterized human basophil rolling and adhesion on HUVECs under physiological shear flow conditions. Interestingly, treatment of endothelial cells with the basophil-specific cytokine IL-3 (0.01-10 ng/ml) promoted basophil and eosinophil, but not neutrophil, rolling and exclusively promoted basophil adhesion. Preincubation of HUVECs with an IL-3R-blocking Ab (CD123) before the addition of IL-3 inhibited basophil rolling and adhesion, implicating IL-3R activation on endothelial cells. Incubation of basophils with neuraminidase completely abolished both rolling and adhesion, indicating the involvement of sialylated structures in the process. Abs to the beta(1) integrins, CD49d and CD49e, as well as to P-selectin and P-selectin glycoprotein ligand 1, inhibited basophil rolling and adhesion. Furthermore, blocking chemokine receptors expressed by basophils, such as CCR2, CCR3, and CCR7, demonstrated that CCR7 was involved in the observed recruitment of basophils. These data provide novel insights into how IL-3, acting directly on endothelium, can cause basophils to preferentially interact with blood vessels under physiological flow conditions and be selectively recruited to sites of inflammation.

Antibodies↗

PubMed2000

[Polynuclear basophils, the key to allergic reactions. Modulations by chemokines].

Both IgE synthesis and inflammatory cell recruitment are recognized to be major components of the allergic response, leading to bronchial inflammation. Typically, T cells are considered to be the key stone of the allergic reaction after acquisition of their TH2 phenotype, responsible for IL-4, -5, -10 -13 production. Basophil is also capable to produce IL-4 and IL-13 following non-specific or antigen activations, and chemokines induce basophil chemotaxis and inflammatory mediator release. However, in context of allergy, the contribution of basophil to cytokine production remains unclear, and the role of chemokine on it is not known. To address this issue, leucocytes from healthy and allergic asthmatic patients were incubated in presence of ionomycine or Ag extracts, with or without chemokine, then fixed, permeabilized, stained using antibodies anti-IgE, anti-CD3, anti-cytokine, and analyzed by flow cytometry. After ionomycin activation, a large majority of basophils from both control and allergic asthmatic subjects express IL-4 and IL-13. Specific antigen induce cytokine expression by 5-20% of basophils from the asthmatic group only, and basophils represent 80% of IL-4 producing cells (p < 0.01). Basophil IL-4 expression peaks at 2 h (p < 0.01), whereas IL-13 expression is more delayed, suggesting that basophil may be involved in initiation, amplification and maintenance of allergic response. Since CD40 ligand is early up-regulated on peripheral blood basophils (p < 0.05), it may be critical in the initial IgE production. CC chemokines (eotaxin, eotaxin-2, RANTES, and MCP-2, 3, 4) enhance the frequency of IL-4 producing basophils (p < 0.01), following Ag activation, and eotaxin lowers the Ag concentration responsible for IL-4 production by 40 fold (p < 0.01). These data demonstrate that after antigen activation, basophils are the predominant peripheral blood cells expressing IL-4 and IL-13, and add weight to the conclusions that basophils are envolved in the regulation of allergic diseases. Finally, our results describe a novel role for CC chemokine: the potentialisation of IL-4 expression, suggesting potential inovative approaches to treat allergic asthma.

Asthma↗

PubMed2006

Signaling transduction pathways involved in basophil adhesion and histamine release.

BACKGROUND: Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles of beta1 and beta2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK) 1/2 in basophil adhesion and histamine release (HR). METHODS: Basophils (purity of 10% - 50%) were preincubated with anti-CD29 or anti-CD18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin (BSA) or fibronectin (Fn) was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay. RESULTS: Basophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin (IL)-3, granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 micromol/L and PP1 at 20 micromol/L strongly interfered with, whereas PD98059 at 50 micromol/L weakly inhibited basophil spontaneous adhesion to Fn. One micromol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 micromol/L partly inhibited anti-IgE induced adhesion. Fifty micromol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE (1:100 or 1:1000) induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 (10 micromol/L, 5 micromol/L) induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient. CONCLUSIONS: Basophil spontaneous adhesion to Fn is mediated by beta1-integrins whereas cytokine induced adhesion to BSA is mediated by beta2-integrins. PI3K, src-kinases and ERK1/2 play distinct signaling roles in basophil adhesion and HR. PI3K is the key player while ERK1/2 is the weakest participant.

Androstadienes↗

PubMed1989

Ultrastructure of monkey peripheral blood basophils stimulated to develop in vivo by recombinant human interleukin 3.

Ultrastructural and cytochemical studies of peripheral blood samples from a monkey continuously infused with recombinant human interleukin 3 were performed. Recombinant human interleukin 3 stimulated a delayed granulocytosis primarily characterized by numerous mature basophils and fewer eosinophils and neutrophils. Basophilic leukocytes were identified by ultrastructural analysis. They were found to be typical granulocytes with polylobed nuclei containing condensed chromatin and numerous cytoplasmic granules. Basophil secretory granules were filled with homogeneous dense contents and were larger than eosinophil and neutrophil secretory granules. Evidence of increased basophil production was accompanied by interleukin 3-associated activation morphologies. These included increased numbers of cytoplasmic and granule-associated vesicles, as are routinely present in a non-IgE-mediated basophil release reaction, termed piecemeal degranulation, and focal perigranular matrix swelling and granule membrane fusion which accompanies anaphylactic degranulation of basophils in other species. Monkey basophils were shown to have a different ultrastructural morphology than that published for monkey mast cells, but exhibited general morphologic criteria for the identification of circulating mature basophils in a number of species. Like human and guinea pig basophils, monkey basophils did not display endogenous peroxidase or peroxidatic activity in a cytochemical assay which simultaneously identified peroxidase-positive granules in neutrophils and eosinophils as well as in synthetic structures in eosinophils. In summary, these studies have identified monkey basophils in an in vivo recombinant human interleukin 3-stimulated model. Interleukin-3 induction of basophilia clearly allowed differentiation of activated mature basophils from eosinophils and neutrophils and mast cells in this species using ultrastructural morphologic criteria.

Animals↗

PubMed1979

Tumor-basophil interactions in vitro--a scanning and transmission electron microscopic study.

Purified guinea pig basophils, or basophils either specifically degranulated with antigen or nonspecifically degranulated with lectin, were cultured with guinea pig line 1 hepatoma cells for 1 to 24 hr and studied ultrastructurally. As early as 1 hr of culture, degranulated or nongranulated basophils and tumor cells formed close contacts by mutually intertwined elongated cell processes and also in cultures containing degranulated basophils, extruded membrane-free basophil cytoplasmic granules became firmly attached to tumor cells. At later intervals, some tumor cells cultured with basophils exhibited cytostatic and cytopathic changes, including dense mitochondria, centralization of organelles, dilated perinuclear and rough endoplasmic cisternae, cell swelling and cytoplasmic lucency, disrupted cytoplasmic organelle and plasma membranes, nuclear pyknosis and fragmentation. Some tumor cell specialized surface attachments were either disrupted or damaged at points of basophil or basophil granule adhesion. Tumor damage was most extensive in cultures containing degranulated basophils, although only a minority of tumor cells (less than 10%) was affected. Tumor injury was seen much less frequently in the presence of nondegranulated basophils, and was absent in control cultures of tumor alone. The occasional viable tumor cells that phagocytosed basophil granules were apparently unharmed, suggesting that internalization of basophil granules by tumor cells is not cytotoxic.

Animals↗

PubMed1995

Identification and partial characterization of a unique marker for human basophils.

A unique marker for human basophils is needed to precisely determine the involvement of this cell type in clinical disease. To search for a marker of the basophil secretory granule, mouse hybridomas were generated against purified human basophils and screened for basophil-selective Ab. One hybridoma (2D7) produced an IgG1 kappa Ab that labeled basophils, but not lymphocytes, monocytes, eosinophils, neutrophils, and mast cells by an indirect immunoperoxidase procedure. The pattern of basophil staining was cytoplasmic and granular by light microscopy. By immunogold electron microscopy, the 2D7 ligand was localized to secretory granules. Activated basophils showed reduced 2D7-dependent staining intensity, consistent with a secretory granule localization. Tissue sections of normal skin, lung, and bowel showed no reactivity with 2D7, consistent with the anticipated absence of basophils in these tissues. 2D7 staining of basophils was clearly distinct from metachromatic staining, which was presumably dependent on proteoglycan. Extracts of normal human basophils subjected to Western blotting with 2D7 exhibited two predominant bands at apparent molecular masses of 76,150 and 72,260 Da. In summary, the 2D7 ligand appears to be a specific marker for human basophils and may facilitate the assessment of basophil involvement in diseases such as asthma, anaphylaxis, and atopic dermatitis.

Animals↗

PubMed2004

Acute basophilic leukemia: case report.

The term "basophilic leukemia" has been in use for 75 years. However, consistent diagnostic criteria are lacking. This is due to the rarity of the disease and to the routine unavailability of special tests that are often required to confirm a diagnosis. We report an unusual case of acute basophilic leukemia in a child who was referred to our Center, arriving with partially treated acute lymphoblastic leukemia. Basophilic differentiation on light microscopy was evident from the coarse basophilic granules in blasts, a progressive maturation of blasts toward basophils, and toluidine positivity on cytochemistry. Blasts showed a myeloid immunophenotype (CD13+, CD33+, CD117+) with a characteristic dual positivity for CD34 and CD25, highly suggestive of basophilic nature of the blasts. Conventional cytogenetic studies revealed translocation t(8;21)(q22;q22). A diagnosis of acute basophilic leukemia with t(8;21) was made. Review of pre-therapy slides showed features consistent with AML-M2 with basophilia. There were no basophilic blasts. With these features, a diagnosis of acute basophilic leukemia secondary to AML-M2 was made. In our patient, basophilic leukemia appears to have evolved from selective clonal proliferation of "basophil-committed blasts" during the course of the disease in a case of AML-M2 with basophilia.

Antigens, CD↗

PubMed2004

Systemic effects of allergen exposure on blood basophil IL-13 secretion and FcepsilonRIbeta.

BACKGROUND: Airway allergen challenge studies have shown the upregulation of cytokines in local airway tissues and distal effects on bone marrow precursors for eosinophils and basophils. OBJECTIVE: We investigated whether local intranasal allergen challenge alters the phenotype of circulating basophils to a primed state. METHODS: Ten subjects with allergic rhinitis were challenged with allergen by means of intranasal spray on 3 sequential days. Basophils were isolated from subjects before challenge and 3, 24, and 96 hours after the third allergen challenge. Basophils were compared before challenge and after the last allergen challenge for levels of FcepsilonRIbeta protein by means of Western blotting and for FcepsilonRIbeta mRNA expression by means of real-time PCR. Basophils were also compared with regard to spontaneous secretion of IL-4 and IL-13. RESULTS: Basophil FcepsilonRIbeta protein levels increased in 5 of 6 subjects after allergen challenge relative to before challenge. Likewise, basophil FcepsilonRIbeta mRNA levels increased a median of 2-fold after the last challenge relative to before challenge ( P=.007, n=9). IL-13 protein was detected in supernatants of 7 of 9 subjects' basophil-enriched cultures after the last challenge compared with 3 of 9 basophil-enriched cultures before challenge (median, 6.2 vs 0 pg/mL; P=.058). IL-4 was not detected in any culture supernatant. CONCLUSION: Intranasal allergen challenge transiently activates circulating basophils by increasing expression of the FcepsilonRIbeta subunit and spontaneous IL-13 secretion. Because FcepsilonRIbeta is an amplifier of FcepsilonRI-mediated responses and IL-13 is proinflammatory, these findings support a primed basophil functional state and demonstrate a systemic effect of local allergen challenge that could contribute in exacerbating allergic reactions.

Administration, Intranasal↗

PubMed1998

Anti-Fc(episilon)RI auto antibodies and basophil histamine releasability in chronic idiopathic urticaria.

BACKGROUND: Circulating functional autoantibodies to the high-affinity IgE receptor (Fc(epsilon)RI) or to IgE have been found in approximately one third of patients with chronic idiopathic urticaria (CIU). OBJECTIVE: We sought to compare basophil histamine release and basophil numbers in patients with CIU with and without autoantibodies. METHODS: Basophil histamine release to the anti-Fc(epsilon)RI mAb 22E7, anti-IgE, and formyl-methionyl-leucyl-phenylalanine (fMLP); basophil numbers; and total cellular histamine were measured in 26 patients with CIU and 18 healthy control subjects. Twelve patients were classified as having functional anti-Fc(epsilon)RI and/or anti-IgE autoantibodies on the basis of their serum-evoked histamine release from the basophils of 2 healthy donors. RESULTS: 22E7 and anti-IgE, but not fMLP, released less histamine from basophils of patients with CIU than from those of control subjects. Mean+/-SEM maximum histamine release to 22E7 from basophils of control subjects and patients with CIU with and without autoantibodies was 38.5%+/-5.0%, 17.9%+/-6.0% (P =.01), and 1.0%+/-0.3% (P <.0001), respectively. Similar results were obtained with anti-IgE, which is dependent on and cross-links cell bound IgE, and 22E7, which directly cross-links the IgE receptor. The mean+/-SEM basophil counts for control subjects and patients with CIU without and with autoantibodies were 52+/-7, 34+/-9 (P =.04), and 5+/-1 (P <.0001) x 10(6) cells/L, respectively, and similar changes were found in measurements of total cellular histamine. CONCLUSION: Patients with autoantibodies have both markedly reduced basophil numbers and basophil histamine release to factors acting through Fc(epsilon)RI, which indicates either a residual pool of functionally distinct basophils or may be a consequence of desensitization of the Fc(epsilon)RI pathway.

Adult↗

PubMed1999

Frequency and characterization of antigen-specific IL-4- and IL-13- producing basophils and T cells in peripheral blood of healthy and asthmatic subjects.

BACKGROUND: Both basophils and T cells are known to secrete IL-4 and IL-13 after activation with either nonspecific stimuli or specific antigen, but the relative contribution of these 2 cell types to overall cytokine production is unclear. OBJECTIVES: To further characterize basophil cytokine production and compare it with that of T cells, we examined the frequency of IL-4- and IL-13-producing basophils and T cells in human PBMCs by means of flow cytometry after activation in allergic asthmatic and normal subjects. METHODS: PBMCs obtained from whole blood after Percoll gradient were activated with specific antigen or ionomycin and fixed. PBMCs were made permeable; stained with antibodies to IgE, CD3, and either IL-4 or IL-13; and analyzed by means of flow cytometry. RESULTS: Preformed cytokines were not detected in unactivated basophils. After ionomycin activation, 60% to 90% of basophils from both control and allergic asthmatic subjects expressed IL-4 and IL-13. Specific antigen induced cytokine expression by 10% to 20% of basophils from the asthmatic group only. After specific antigen activation, basophils accounted for 4 times more IL-4-producing cells than did T cells. IL-4 and IL-13 production at 2 hours was exclusively from basophils. After allergen activation, CD40 ligand was upregulated on a subset of peripheral blood basophils. CONCLUSIONS: These data demonstrate that basophils are the predominant peripheral blood cells that express IL-4 and IL-13 in the first 6 hours after antigen activation and strengthen the putative role of basophils both in IgE production and in the generation of allergic inflammation.

Adult↗

PubMed1998

Characterization of protein serine/threonine phosphatase activities in human lung mast cells and basophils.

1. The serine/threonine protein phosphatase (PP) inhibitors, okadaic acid and calyculin, attenuated the IgE-mediated release of histamine from human lung mast cells (HLMC) and basophils in a dose-dependent manner whereas an alternative PP inhibitor, microcystin, was ineffective. Calyculin was more potent than okadaic acid in both cell types. The concentration required to inhibit by 50% (IC50) the release of histamine was 15 (HLMC) and 50 nM (basophils) for calyculin and 200 (HLMC) and 300 nM (basophils) for okadaic acid. 2. Lysates of purified HLMC and basophils dephosphorylated radiolabelled glycogen phosphorylase, a substrate for both PP1 and PP2A. The PP activity in lysates of both cell types was inhibited in a dose-dependent fashion by the PP inhibitors with the following rank order of activity, calyculin (approximate IC50; 0.02-0.1 nM) > or = microcystin (0.1 nM) > okadaic acid (70 nM). 3. The PP1-selective inhibitor, inhibitor-2 (I-2), attenuated the dephosphorylation of glycogen phosphorylase in lysates of both HLMC and basophils. I-2 (20 nM) inhibited the glycogen phosphorylase PP activity by 71+/-3% and 49+/-13% in HLMC and basophil extracts, respectively. There were, approximately, 6 fold greater levels of I-2-sensitive activity in HLMC than in basophils. Qualitatively similar results were obtained with an alternative PP1-selective inhibitor, inhibitor-1 (I-1). 4. Lysates derived from HLMC and basophils dephosphorylated radiolabelled casein which is a PP2A-restricted substrate. HLMC lysates contained, approximately, 2.5 fold higher levels of casein PP activity than basophil lysates. 5. These data indicate that HLMC and basophils both contain PP1 and PP2A. The data suggest that, on a per cell basis, HLMC have higher levels of both PP1 and PP2A. Moreover, the ratio of PP1 to PP2A is higher in HLMC than in basophils.

Basophils↗

PubMed1982

Formation of Charcot-Leyden crystals by human basophils.

Charcot-Leyden crystals (CLC) are currently believed to be unique to the eosinophil and a hallmark of active eosinophilic inflammation or proliferation. The distinctiveness of the CLC to the eosinophil was questioned in 1965 by Archer and Blackwood (9), but their demonstration of CLC formation in basophils was ignored and later dismissed (1) as being the result of eosinophil contamination of basophil-enriched cell suspensions. We reexamined this question and showed that basophils obtained from the peripheral blood of normal individuals form CLC and that basophils contain a protein that is immunochemically indistinguishable from eosinophil CLC protein. These conclusions are based upon the findings that (a) crystal formation in basophils was demonstrated by specific histochemical staining of crystal-containing cells in highly enriched basophil suspensions prepared by fluorescence-activated cell sorter (FACS) purification of surface IgE-positive cells, (b) that enrichment for surface IgE-positive cells (primarily basophils) by the FACS also enriched for cells staining positively by immunofluorescence for eosinophil CLC protein, and (c) that CLC protein was measured by radioimmunoassay in cell extracts prepared from purified basophil suspensions containing 97-99% basophils and absolutely no contaminating eosinophils. These basophil extracts contained a protein immunochemically indistinguishable from eosinophil CLC protein. Based upon these findings, the CLC or the protein comprising the crystal (lysophospholipase) can no longer be considered as distinctive to the eosinophil. We must now consider the possibility that the presence of CLC in tissues, sputum, or stool may also represent basophil involvement in disease processes.

Animals↗

PubMed2006

Trans-basement membrane migration of human basophils: role of matrix metalloproteinase-9.

In allergic disorders, basophils migrate from the blood stream to inflamed tissue sites. Since trans-basement membrane migration is an important step for local basophil accumulation, we performed a human basophil transmigration assay using a model basement membrane, Matrigel. IL-3 in the upper chamber was critical for basophil trans-basement membrane migration over baseline levels, since none of the chemoattractants placed in the lower chambers induced migration. RANTES, IL-8, 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) and platelet-activating factor (PAF) significantly up-regulated the transmigration of IL-3-treated basophils. Neutralizing experiments indicated the involvement of beta2 integrin and matrix metalloproteinase (MMP)-2/9 in basophil transmigration. Real-time quantitative PCR revealed that basophils constitutively expressed transcripts for MMP-9, and at lower levels, MMP-2, but cell-surface expression was only detected for MMP-9. MMP-9 was also detected in the cytoplasm and culture supernatant of the basophils. Treatment with IL-3 up-regulated the surface level of MMP-9 on the basophils. Our results suggest that basophils possess a unique regulatory mechanism for trans-basement membrane migration which is affected by cytokines, chemoattractants, beta2 integrin and MMPs, especially MMP-9. MMP-9 may be critically involved in the pathogenesis of local basophil influx in allergic diseases.

Basement Membrane↗

PubMed2004

Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2.

BACKGROUND: Both prostaglandin (PG) D receptor (DP) and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells)/DP2 are high-affinity receptors for PGD2. Previous studies have demonstrated that PGD2 enhances releasability and induces CRTH2/DP2-mediated migration in human basophils, but the precise effects of PGD2 on basophils as well as receptor usage have not been fully clarified. OBJECTIVE: We comprehensively explored the roles of DP and CRTH2/DP2 in basophil functions by using selective agonists and antagonists for each receptor. METHODS: DP and CRTH2/DP2 transcripts were quantified by real-time PCR. We studied the effects of selective agonists (DP: BW245C; CRTH2/DP2: 13,14-dihydro-15-keto (DK)-PGD2) and/or antagonists (DP: BWA868C; CRTH2/DP2: ramatroban) on Ca2+ mobilization, migration, degranulation, CD11b expression and survival of human basophils. RESULTS: Basophils expressed transcripts of both DP and CRTH2/DP2, but the levels of CRTH2/DP2 transcripts were ca. 100-fold higher compared with DP transcripts. Ca2+ influx was induced in basophils by either PGD2 or DK-PGD2/CRTH2 agonist but not by BW245C/DP agonist. Basophils treated with PGD2 were completely desensitized to subsequent stimulation with DK-PGD2, but not vice versa. DK-PGD2 as well as PGD2 up-regulated CD11b expression, induced migration and enhanced degranulation, and those effects were completely antagonized by ramatroban/CRTH2 antagonist. In contrast, BW245C/DP agonist exhibited an inhibitory effect on basophil migration and IgE-mediated degranulation, and the migration inhibitory effect was effectively antagonized by BWA868C/DP antagonist. On the other hand, while PGD2 significantly shortened the basophil life-span, neither DK-PGD2/CRTH2 agonist nor BW245C/DP agonist did. CONCLUSION: CRTH2/DP2 is primarily responsible for the pro-inflammatory effects of PGD2 on human basophils, while DP introduces negative signals capable of antagonizing the effects of CRTH2/DP2 in these cells. The effects of PGD2 on longevity imply a mechanism(s) other than via DP or CRTH2/DP2. CRTH2/DP2 on basophils may afford opportunities for therapeutic targeting in allergic inflammation.

Basophils↗

PubMed1987

Differences in the kinetics of histamine formation and granulation of human basophilic cells from bone marrow, peripheral blood, and cord blood.

Human bone marrow, cord blood, and peripheral blood contain progenitor cells, which during culture mature to histamine-containing basophilic cells. In bone marrow the histamine content per Alcian blue staining basophilic cell was low before culture. Cultivation of BML cells resulted in increased histamine levels in cultures (P less than 0.05), whereas the basophilic cells did not increase significantly. Cell cultures were stimulated with conditioned medium (CM) produced with allergen-stimulated cells from atopics and from the Mo T leukaemic cell line. Cells from cultures stimulated with CM contained less histamine calculated per basophilic cell than did those from unstimulated cultures (P less than 0.05). There was a significant correlation between the numbers of basophilic cells and the histamine content in cells on day 0 prior to cultivation and after 14 days of cultivation (P less than 0.01 and P less than 0.05 respectively). In cord blood there was a correlation between the numbers of basophilic cells and the histamine levels prior to cultivation (P less than 0.05). During cultivation the number of basophilic cells increased five-fold (P less than 0.02), whereas the histamine levels did not increase resulting in a decreased histamine level per basophilic cell (P less than 0.02). In peripheral blood the basophilic cells contained the highest levels of histamine. The numbers of basophilic cells and their content of histamine showed good correlation both before and after unstimulated and stimulated cultivation (P less than 0.01), whereas unstimulated cultures did not show such correlation. The results indicate the presence of different proportions of progenitor cells in bone marrow, cord blood, and peripheral blood, all with different ability to produce histamine and become granulated basophilic cells.

Allergens↗

PubMed2006

Expression and functions of the vascular endothelial growth factors and their receptors in human basophils.

Angiogenesis is a multistep complex phenomenon critical for several inflammatory and neoplastic disorders. Basophils, normally confined to peripheral blood, can infiltrate the sites of chronic inflammation. In an attempt to obtain insights into the mechanism(s) underlying human basophil chemotaxis and its role in inflammation, we have characterized the expression and function of vascular endothelial growth factors (VEGFs) and their receptors in these cells. Basophils express mRNA for three isoforms of VEGF-A (121, 165, and 189) and two isoforms of VEGF-B (167 and 186). Peripheral blood and basophils in nasal polyps contain VEGF-A localized in secretory granules. The concentration of VEGF-A in basophils was 144.4 +/- 10.8 pg/10(6) cells. Immunologic activation of basophils induced the release of VEGF-A. VEGF-A (10-500 ng/ml) induced basophil chemotaxis. Supernatants of activated basophils induced an angiogenic response in the chick embryo chorioallantoic membrane that was inhibited by an anti-VEGF-A Ab. The tyrosine kinase VEGFR-2 (VEGFR-2/KDR) mRNA was expressed in basophils. These cells also expressed mRNA for the soluble form of VEGFR-1 and neuropilin (NRP)1 and NRP2. Flow cytometric analysis indicated that basophils express epitopes recognized by mAbs against the extracellular domains of VEGFR-2, NRP1, and NRP2. Our data suggest that basophils could play a role in angiogenesis and inflammation through the expression of several forms of VEGF and their receptors.

Adult↗

PubMed1975

Chemotaxis of basophils by lymphocyte-dependent and lymphocyte-independent mechanisms.

Guine pigs basophils obtained from blood or bone marrow have been studied for their chemotactic responsiveness. Chemotactic factors for basophils include a substance (lymphokine) present in culture fluids from antigen-stimulated lymphocytes, a material generated in zymosan-activated guinea pig serum, a C5 cleavage factor, and a bacterial factor. When compared with homologous neutrophils and monocytes, basophils respond most rapidly to a chemotactic stimulus. The lymphokine basophil chemotactic factor is physicochemically similar to the previously described monocyte chemotactic factor but appears to be distinct from it as well as MIF and neutrophil chemotactic factor present in the same fluids, Part of the evidence for this is the ability to detect basophil chemotactic factor in the absence of other lymphokine activities under appropriate experimental conditions. More evidence, specifically relating to the monocyte factor, is that monocytes can adsorb basophil chemotactic activity but not vice versa. This latter observation may have implications for the mechanism whereby the accumulation of basophils is controlled and limited in vivo. In addition, it was noted that specific antigen could also suppress basophil chemotaxis. Although the mechanism of this phenomenon is unclear, it could serve as a second means by which basophil accumulation may be controlled in the intact animal. Taken together, these observations provide further definition of the chemotactic behavior of basophils in general, and underscore some of the ways in which lymphocytes can influence basophils through lymphokine-dependent mechanisms.

Animals↗

PubMed1986

Metabolic comparison between basophils and other leukocytes from human blood.

Basophilic granulocytes were purified from the blood of normal individuals by successive isopyknic centrifugation and elutriation centrifugation. Starting with the leukocyte-rich fraction of 500 ml of blood, we recovered 31 to 80% (mean 51%, n = 20) of the basophils in 45 to 87% purity (mean 69%, n = 23). The contaminating cells were mainly lymphocytes. The basophils were greater than 98% vital (exclusion of ethidium bromide and hydrolysis of fluorescein diacetate). The histamine content of the basophils was 1.1 to 2 pg/cell (mean 1.6 pg/cell, n = 22). With anti-IgE, 30 to 50% of the histamine was released; with phorbol myristic acetate (PMA) or the calcium ionophore A23187, 70 to 100% of the histamine was released. Serum-opsonized zymosan (STZ) did not induce histamine release. Reactions with monoclonal antibodies revealed that the basophils expressed the C3bi receptor (CR3) and the leukocyte function-associated antigen 1 (LFA1), but not the gp 150,95 antigen, the C3b receptor (CR1), or the low avidity Fc gamma receptor. Basophils carry class I but not class II HLA antigens. During incubation of the basophils with serum-opsonized Staphylococcus aureus or Escherichia coli, these bacteria were neither phagocytized nor killed. STZ, PMA, A23187, or anti-IgE did not initiate an "oxidative burst" in the basophils. This was tested with oxygen consumption, cytochrome c reduction, NBT reduction, chemiluminescence, and release of hydrogen peroxide. Moreover, we did not detect cytochrome b558, superoxide dismutase, catalase, or peroxidase in the basophils. Of the typical granule-associated enzymes lysozyme, Vitamin B12-binding protein, and beta-glucuronidase, only beta-glucuronidase was present in the basophils in detectable amounts. This enzyme was released, together with histamine, on incubation of the cells with PMA, A23187, or anti-IgE, but not with STZ. We conclude that basophils from normal human blood are not phagocytes and are probably not involved in the oxidative defense of the host against foreign antigens.

5'-Nucleotidase↗