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At least 19 recordsLinked to original sources
PubMed1978

Cutaneous basophil anaphylaxis. Immediate vasopermeability increases and anaphylactic degranulation of basophils at delayed hypersensitivity reactions challenged with additional antigen.

Many delayed-type reactions contain large infiltrates of basophils whose function is unknown. We have studied these cutaneous basophil hypersensitivity (CBH) reactions in guinea-pigs to ascertain whether basophils that are recruited to delayed reaction sites could be triggered for immediate reactivity. We compared 24 h CBH reactions with nearby skin for immediate hypersensitivity by challenging each site with small amounts of antigen. CBH sites had augmented immediate increases in vascular permeability detected by extravasation of Evan's blue dye. The ability to elicit this augmented anaphylactic phenomenon correlated with the local presence of basophils, and light microscopy at CBH reactions 15 min after antigen challenge showed a 50% decline in basophil counts. Electron microscopy showed that progressive anaphylactic-type degranulation of local basophils occurred within minutes following reintroduction of antigen. There was fusion of vacuoles containing granules, exocytosis of granules, and dissolution of granules, without ultrastructural disruption of cellular integrity. These results establish that basophils in CBH reactions can be triggered with soluble antigen to undergo anaphylactic degranulation, with the immediate release of vasoactive mediators. We have termed this phenomenon 'cutaneous basophil anaphylaxis'. Thus, one function of basophils at sites of delayed hypersensitivity may be to provide the potential for augmented, local, immediate anaphylactic reactivity.

Anaphylaxis↗
PubMed1979

Ultrastructure of basophilic leukocytes and mast cells in normal and cutaneous basophil hypersensitivity-reacted guinea pig dermis.

Basophilic leukocytes and mast cells in guinea pig dermis in normal and cutaneous basophil hypersensitivity (CBH) reaction were examined by light and electron microscopy. Basophils were rare in the normal dermis and predominantly revealed in the CBH-reacted skin. Some infiltrating basophils of the reacted displayed an immediate attachment to mast cells. Cytoplasmic continuities were partially seen between them. They were most plentiful at 48 h after phytohemagglutinin injection and decreased in number thereafter. The basophils contained three types of granule. The vast majority of granules were Type I granules, basophil-specific granules. Type II granules were less frequently encountered and resembled a mast cell granule in the fine structure. Type III granules were scant and small-cored vesicles.

Animals↗
PubMed1975

Specificity of basophils and lymphocytes in cutaneous basophil hypersensitivity.

Using a rosetting technique, it was found that the vast majority of basophils circulating in the blood or accumulating in the skin reactions of guinea pigs primed for cutaneous basophil hypersensitivity (CBH) lacked demonstrable specificity for sensitizing antigen, whether sheep erythrocytes, a soluble protein, or tumor cells. By contrast, one-third of cells teased from late skin reactions formed specific rosettes as did nearly 80% of circulating basophils in animals receiving repeated doses of whole sheep blood. Unreactive basophils teased from CBH reactions readily acquired rosetting capacity on exposure to immune serum. With regard to lymphocyte (and hence reaction) specificity, both CBH and classic delayed hypersensitivity (DH) reactions exhibited a high degree of carrier specificity when dinitrophenyl-conjugates were used. Thus, in the hapten-carrier combinations examined thus far, the antigen skin test requirements for both CBH and DH have been identical and are those required for inducing an active lymphocyte response. These findings indicate that control mechanisms other than homocytotropic antibodies must be sought to explain the accumulation and behavior of basophils in CBH reactions and, coupled with other data, suggest that lymphocytes and/or their products are likely candidates for this role.

Animals↗
PubMed1977

A simplified method for measuring basophil histamine release and blocking antibodies in hay fever patients. Basophil histamine content and cell preservation.

A simplified method for measuring basophil histamine release in grass pollen hay fever patients has been developed. Leukocytes were challenged in vitro with extracts of Phleum pratense (timothy) and the release of histamine was determined indirectly as the residual histamine in the cell sediment. Several steps to purify histamine thus became superfluous and histamine was directly conjugated with o-phthaldialdehyde to form a fluorophore. The simplified method showed a basophil histamine content which was in accordance with results obtained by more specific methods. No difference in basophil histamine content was found between normal and allergic persons. For the histamine liberation assay blood could be adequately preserved for transport for 48 h at room temperature by adding cell culture medium. Basophil histamine release technique allows evaluation of cell sensitivity for determination of the degree of allergy as well as the level of blocking antibodies.

Adult↗
PubMed1978

Basophil histamine release by RNA, DNA and aggregated IgG examined in rheumatoid arthritis and systemic lupus erythematosus. Results compared with basophil counts and antinuclear antibodies.

Basophils from patients with rheumatoid arthritis (RA) respond to RNA, DNA and immune complexes (aggregated IgG) with histamine release. The RNA response was well correlated to the clinical activity of the disease, since histamine liberation was found in all patients with severe activity, whereas no liberation was observed in patients with moderate or quiescent activity. A less significant correlation was obtained with DNA and aggregated IgG. In contrast, no response was obtained with RNA, DNA and aggregated IgG in patients with systemic lupus erythematosus (SLE) or in controls. In the RA and the SLE groups no significant correlation was found between the response of RNA, DNA and aggregated IgG and the serum titres of anti-DNA and antinuclear antibodies. No difference in basophil cell count in peripheral blood and basophil histamine content was found between RA, SLE and controls. Our results point to an involvement of an autoimmune type I reaction in the pathogenesis of RA directed against the nuclear components RNA and DNA and against immune complexes.

Adolescent↗
PubMed2026

Tumor-Infiltrating Basophils Are Associated With Improved Prognosis in Colorectal Cancer.

PURPOSE: Basophils are rare granulocytic cells known for their role in allergic reactions, but they may also be involved in other diseases such as cancer. However, the role of tumor-infiltrating basophils in colorectal cancer (CRC) remains unexplored. Here, we aimed to clarify the significance of basophils in CRC by analyzing tumor tissue from 2 CRC cohorts (n = 1830) and blood samples from 730 patients. MATERIALS AND METHODS: Tumor-infiltrating basophils were identified and quantified using double immunohistochemistry (proMBP1 for basophils and cytokeratin for tumor cells) combined with digital image analysis, and blood basophil counts were measured. The associations between basophils (in tumor tissue and blood) and clinicopathological features, prognosis, immune cell profiles, and systemic inflammation markers were examined. RESULTS: Higher densities of tumor-infiltrating basophils showed an inverse association with cancer-specific mortality, with stronger evidence in cohort 2 than in cohort 1. After adjusting for key prognostic factors (including disease stage and mismatch repair status), the hazard ratios for cancer-specific mortality comparing high versus low basophil density were 0.67 (95% CI, 0.43-1.03; Ptrend = .051) in cohort 1 (n = 749) and 0.54 (95% CI, 0.40-0.74; Ptrend < .001) in cohort 2 (n = 1039). Higher basophil densities were also associated with lower disease stage and less frequent lymphovascular invasion but not with mismatch repair deficiency. Blood basophil count correlated with tumor-infiltrating basophil density (r = 0.113; P = .003) but not with prognosis. CONCLUSIONS: Tumor-infiltrating basophils seem to be associated with favorable clinicopathological features and potentially improved CRC outcomes, suggesting that basophils may contribute to the tumor microenvironment.

Humans↗
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↗
PubMed1977

Cuta neous basophil responses in neonatal guinea pigs: active immunization, hapten specific transfer with small amounts of serum, and preferential elicitation with phytohemagglutinin skin testing.

Previous studies have demonstrated a failure to elicit delayed hypersensitivity skin responses in neonatal guinea pigs despite apparent immunologic competence of their lymphocytes and monocytes. The ability of neonatal guinea pigs to manifest cutaneous basophil hypersensitivity (CBH) responses was examined. Neonates were competent to express macroscopic and microscopic aspects of these delayed reactions. Strong cutaneous basophil responses were elicited in newborns (0 to 2 days old) in a hapten-specific manner after intravenous transfer of small amounts of immune serum (0.5 ml) obtained from adult donors. Also, neonatal guinea pigs actively immunized at birth with hapten-carrier conjugates emulsified with incomplete Freund's adjuvant (IFA) and skin tested when 1 week old had 24-hr hapten-specific cutaneous basophil reactions and CBH reactions to the carrier protein as well. Compared with adult CBH reactions, neonatal responses had equal concentrations of basophils, fewer monocuclear cells, less macroscopic erythema, and almost no induration. Hapten-specific CBH reactions also contained significant infiltrates of eosinophils which were more prominent in the ear skin vs flank skin and in neonates vs adults. Immunization with complete Freund's adjuvant (CFA) resulted in a marked difference between adults and neonates; adult PPD reactions were quite indurated and contained many more monoculear cells and few basophils, whereas neonatal PPD reactions were flat, erythematous, nonindurated, and contained relatively few mononuclear cells and more basophils. Thus, neonatal tuberculin reactions elicited by PPD in animals immunized with CFA were examples of CBH. Skin testing nonimmune guinea pigs with phytohemagglutinin (PHA) also revealed marked differences in 24-hr cutaneous reactions between adults and newborns. Adults had indurated and erythematous reactions which contained approximately 20% basophils and 80% mononuclear cells, whereas similar PHA skin tests in newborns elicited small macroscopic reactions, which microscopically showed large infiltrates containing approximately 80% basophils and 20% mononuclear cells. It was concluded that neonatal guinea pigs were not only competent to manifest basophil-containig delayed-type reactions, but that cutaneous basophil responses were preferentially elicited in these animals under a variety of circumstances. These results underline the fact that basophil accumulations are one aspect of delayed skin test responses and that the regulation of the arrival of these cells in neonates is different from that in adult guinea pigs.

Animals↗
PubMed1977

Study of possible mechanisms of basophil accumulation in experimental cutaneous candidiasis in guinea pigs.

It is known that certain lymphokine preparations, bacterial growth products, and factors released through complement activation have in vitro chemotactic activity for basophils. We have developed a model for acute cutaneous candidiasis in guinea pigs in which the lesions are characterized by infecting organisms in the keratin layer, early accumulation of polymorphonuclear leukocytes in the upper epidermis, and subsequent accumulation of basophils along the dermal basement membrane. The present study was undertaken to determine if any of the known chemotactic factors were operating in vivo to attract basophils. Both nonimmune guinea pigs and animals with established delayed hypersensitivity to candida had basophils in the infected skin. While immune animals showed more basophils than did nonimmune animals, the difference was not significant. Intradermal injections of a sonicate of candida or a candida growth filtrate did not cause significant accumulation of basophils. Decomplementation of the animals with cobra venom factor (CVF) did not significantly reduce the basophil numbers. Moreover, basophil accumulation occurred in animals with only minimal serum antibody to candida. These studies indicate that the basophil accumulation is due to a mechanism that is not dependent on cellular immunity, direct chemotactic activity in the candida extract, antibodies, or complement. Therefore, there may exist a previously unrecognized, nonimmunologic mechanism of chemotaxis for basophils which could possibly operate in other types of lesions and could even be involved with attraction of other types of cells.

Animals↗
PubMed1975

Basophil counting with a new staining method using alcian blue.

Difficulties in obtaining reproducible and accurate enumeration of circulating basophils with existing techniques have hampered investigation of this infrequent cell population. A new basophil staining method is described that employs alcian blue dye for staining of heparin within basophils at low pH and in the presence of lanthanum ions. Basophil recognition is facilitated by reducing nonspecific nuclear staining. This objective is achieved because of the differences in stability of alcian blue-heparin, alcian blue-nucleic acid, lanthanum-heparin, and lanthanum-mucliec acid complexes. Reduction of pH after staining also favors solubilization of leukocyte cytoplasmic proteins, providing greater contrast between stained and unstained cells by reducing light scattering of the unstained leukocytes . The alcian blue staining method is suitable both for chamber basophil counting and automated basophil counting using continuous-flow sampling and electro-optical detection. The new staining method was evaluated by comparing it with the chamber counting method using toluidine blue in a triple-blind study in which the results of basophil counting by the alcian blue chamber method, alcian blue automated instrument method, and the toluidine blue chamber method were analyzed for reproducibility and compared with an indirect basophil count obtained from a 1000-cell leukocyte differential and a total leukocyte count. Both alcian blue staining methods gave greater reporducibility that toluidine blue and were more accurate, as evidinced by a significantly higher correlation with the indirect basophil count. The improved reproducibility, accuracy, and convenience of this method over existing methods should facilitate the collection of more meaningful information about circulating basophil levels in health and disease.

Alcian Blue↗
PubMed1976

Circulating basophils in normal subjects and in subjects with hay fever.

The relationship of hay fever symptoms and changes in the number of circulating basophils was studied in 12 subjects clinically sensitive only to ragweed and in 10 nonatopic subjects before, during, and after the ragweed season. Total white blood counts, absolute basophil counts, and symptom scores were recorded twice weekly from mid-June through October, 1974, and compared with the ragweed pollen count. The results indicated that the absolute and relative number of basophils were significantly elevated (p less than 0.001) in the hay fever group when symptoms occurred. As the symptom score of the allergic group increased during the ragweed season, the number of basophils also increased, only to decrease to control values when symptoms subsided. The basophil counts of the atopic group were significantly higher than those of the nonatopic group during the control periods. The nonatopic group also showed a significant elevation of basophils during the ragweed season, but to a much lesser extent than the atopic group. It is concluded that: (1) subjects with symptomatic hay fever have a significantly elevated absolute and relative basophil count which correlates with the exacerbation and remission of symptoms; (2) nonatopic subjects also have a small but significant elevation of basophils during the ragweed season; and (3) the elevation of basophils in the atopic group during symptoms is significantly greater than in the nonatopic group during the ragweed season.

Adolescent↗
PubMed1976

Demonstration of reaginic antibodies on human basophils by immune adherence to allergen-coated Sepharose beads.

Human basophils purified by gradient density centrifugation and differential glass bead adherence were interacted with grass pollen allergen in particulate form prepared by covalent coupling of Dactylis glomerata protein concentrate to Sepharose beads. Basophils from allergic subjects were found to interact specifically with the allergen-coated bead surface in a manner so highly characteristic that false negatives with basophils from non-allergic subjects or subjects with unrelated allergies were not encountered. Microscopic examination indicated that the specifically stained malleable basophils had adapted in a multi-point attachment to the rigid bead surface by becoming one-sidedly flattened against it. When using basophils from highly pollen sensitive subjects all the beads carried basophils and sometimes as many as thirty per bead. The percentage of beads with basophils and the number of basophils per bead roughly correlated with clinical history and skin tests. Immunocytoadherence of the basophils to the allergen-coated beads was specifically inhibited by anti-IgE and anti-allergen antibodies, including reagins.

Allergens↗
PubMed1976

Basophils in tuberculin and "Jones-Mote" delayed reactions of humans.

Jones-Mote reactions are delayed, erythematous, and mildly indurated cutaneous reactions originally described in humans sensitized by skin injection of heterologous proteins. Similar reactions in guinea pigs contain many basophils and are called cutaneous basophil hypersensitivity. In contrast, guinea pigs immunized with mycobacterial adjuvants have classical tuberculin-type delayed hypersensitivity reactions, which contain few basophils. This has led to a new classification of delayed responses, based largely on the presence or absence of basophils. We induced sensitization for Jones-Mote reactions in 20 normal humans by intradermal injections of keyhole limpet hemocyanin. Skin tests with KLH 1 wk later showed erythematous and indurated delyaed reactions in all subjects. Rebuck skin windows showed specific accumulations of basophils with a delayed time-course in 18 of 20 subjects. In 12 normals sensitized with oxazolone-keyhole limpet hemocyanin conjugates, skin reactions and in vitro lymphocyte stimulation showed carrier and not hapten specificity, suggesting that cutaneous responses were probably mediated by T cells. A comparative study of strongly positive PPD skin tests in patients with tuberculosis showed significant basophil accumulations in five of nine subjects. Thus, basophils occurred in human tuberculin and Jones-Mote reactions and were not a distinguishing feature of Jones-Mote reactions. We suggest that the occurrence of basophils at delayed reactions is under complex regulation and that basophil accumulations are an aspect of delayed hypersensitivity, rather than an indication of a distinctive and separate response.

Adult↗
PubMed1977

The antigen-induced degranulation of basophil leukocytes from atopic subjects studied by electron microscopy.

Suspensions of washed leukocytes were prepared from the blood of atopic subjects and incubated with diluent, ragweed antigen E or rye grass group I antigen. Histamine release into the suspending medium was measured and directly correlated with changes in the ultrastructure of basophil leukocytes from the same tubes. Incubation of leukocytes with either diluent or an antigen to which the donor was not hypersensitive caused no significant histamine release and the morphology of the basophils was unaltered. By contrast, incubation of leukocytes with an intigen to which the donor was hypersensitive caused substantial histamine release and characteristic morphologic changes in the basophils, many of which underwent exocytotic degranulation. Degranulated human basophils showed the following features: (1) an irregular surface, to which platelets and leukocytes were often adherent; (2) reduction in the number of basophilic granules; (3) residual granular material, both in exocytotic cavities and at the cell surface; (4) coated vesicles and cisternae of smooth endoplasmic reticulum, frequently related to the plasma membrane at sites of exocytosis; (5) thin membrane-bounded granules appeared unaltered; (6) no consistent change was observed in centrioles, microtubules, 90 A filaments, mitochondria, or multivesicular bodies, and degranulated basophils appeared ultrastructurally viable; (7) in reaction cell suspensions, nondegranulated basophils often showed a more active contour than control cells; both reacting but nondegranulated basophils and degranulated basophils sometimes showed localized filamentous webs at their periphery.

Antigens↗
PubMed1975

[Quantitation of basophil cell-line in human bone marrow (author's transl)].

Appropriately fixed basophil cell-line can selectively be visualized by anionic dyes as toluidine blue. Typical activities for Leder's esterase distinguish individual maturity stages. Both methods were successively applied to bone marrow smears from 22 healthy subjects in order to assess the basophil population among the total marrow leukocytes (lymphocytes, monocytes and granulopoietic cell-lines) and the portion of each basophil maturity stages. Total basophils represent 0.45+/-0.13% of marrow leukocytes. Basophil precursors capable of division (promyelocytes and myelocytes) comprise 46.7%, mitoses 3.7+/-1.76% of the total marrow basophil population. The frequency distribution of these subpopulations approximated a normal distribution pattern. No clear central tendencies could be encountered in the dispersion of other stages. The low peripheral basophil counts, the high incidence of divisible precursors and the considerable mitotic activity suggest a short half-life time for blood basophils.

Basophils↗
PubMed1979

Mechanisms of hypersensitivity: cellular interactions. Basophil arrival and function in tissue hypersensitivity reactions.

Bone marrow-derived blood basophils are recruited into the tissues by immuno mechanisms in a variety of delayed time-course hypersensitivity responses. In the skin these are called cutaneous basophil hypersensitivity (CBH) reactions. In guinea pigs, it is now established that the elicitation of CBH is dependent on T cell- and/or (antibody)-triggered mechanisms. Both are subject to modulation. T cell-mediated CBH seems to be suppressed in basophil-poor tuberculin-type reactions. B cells mediate CBH via antibody of IgG1 isotype through mechanisms that involve Fc receptors, which can be competitively blocked. After basophils arrive at a CBH reaction they can be triggered by antigen to immediately release mediators such as histamine. Thus, one consequence of the arrival and accumulation of basophils at delayed hypersensitivity reactions is to augment the anaphylactic potential of a given tissue site. In reactions to parasites, release of mediators by tissue basophils seems to aid in the expulsion of these multicellular organisms, In addition, histamine released by recruited basophils, or by locally resident mast cells, may modulate some delayed reactions through stimulation of histamine-2 receptors on cells such as T lymphocytes. In mice, mast cell release of serotonin and subsequent stimulation of the local vasculature seems to be required to allow diapedesis and tissue accumulation of various bone marrow-derived accessory leukocytes in delayed-type hypersensitivity responses. Thus, basophils and mast cells, and their release of mediators such as vasoactive amines, are involved in the onset, development, and function of various tissue hypersensitivity responses.

Anaphylaxis↗
PubMed1979

Basophil chemotaxis under agarose: variability among guinea pig donors and response to sera of different species.

Guinea pig basophils were tested against chemotactic factor(s) generated from homologous and heterologous sera. An "under agarose" method of quantitating leukocyte chemotaxis was adapted to measure serum-derived basophil chemotactic factor(s) (BCF). The method was found to be simple, reproducible, and sparing of time and reagents and it provided simultaneous controls. Because of the economy of reagents compared with the Boyden chamber technique, basophils from individual guinea pigs could be studied and were found to be variable in responsiveness. A definite difference in the response of guinea pig basophils to zymosan-activated sera of various other species was demonstrated. Guinea pig basophils responded to zymosan-activated serum from guinea pig and rat but failed to respond to zymosan-activated serum from human, hamster, rabbit, or cow. Optimal conditions were determined for cell numbers, serum activation and dilution, and migration times for studies of guinea pig BCF. The under agarose technique provides a practical alternative to chamber methods for the study of basophil chemotaxis. Although guinea pig basophils do not respond to human serum-derived BCF, the economy of reagents with this technique gives promise toward adaptation of the method to studies of human basophil chemotaxis.

Animals↗