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C A Dahinden

Publications and source records attributed to C A Dahinden.

At least 19 recordsLinked to original sources
PubMed1999

Regulation of cytokine expression and leukotriene formation in human basophils by growth factors, chemokines and chemotactic agonists.

Basophils stimulated with IL-3 plus C5a selectively express IL-4 and IL-13 and continuously produce leukotrienes (LT) for hours. C5a combined with IL-5 or granulocyte-macrophage colony-stimulated factor was, however, much less effective in promoting cytokine expression and a late continuous phase of LTC4 production, possibly due to lower expression levels of their receptor alpha chains. Basophils also express several chemoattractant receptors, including high levels of C5a receptors, macrophage chemotactic protein (MCP) receptors (CCR2) and eotaxin receptors (CCR3), intermediate levels of CXCR1, CXCR2 and platelet-activating factor receptors, and lower levels of N-formyl-Met-Leu-Phe (fMLP) receptors. However, among the corresponding agonists, only C5a, fMLP and much more weakly MCP1, were found to induce cytokine expression and continuous LTC4 release, and only when combined with IL-3. CCR3, which is highly expressed on basophils and has been shown to mediate strong migratory but weak release responses, does not regulate cytokine expression. The weakly expressed fMLP receptor is an efficient activator of several cell functions including LTC4 formation, while CXCR2 hardly affects basophil function despite considerable expression. Thus, chemoattractant-receptors mediate different cellular responses unrelated to their expression levels.

Basophils↗
PubMed1999

Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa.

BACKGROUND: The beta chemokine monocyte chemotactic protein 3 (MCP-3) has chemoattractant and activating capabilities in monocytes, lymphocytes, eosinophils, and basophils. AIMS: To investigate MCP-3 expression in inflammatory conditions of the human intestinal mucosa. PATIENTS: Forty five colon biopsy specimens from 18 patients with inflammatory bowel disease (IBD; 16 specimens from inflamed and 10 from non-inflamed areas) and 19 control patients were examined. METHODS: Immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) were used for MCP-3 detection in tissue sections. Intestinal epithelial cell lines (HT-29, Caco-2, T-84) were stimulated with interleukin (IL) 1beta, IL-6, and tumour necrosis factor alpha (TNF-alpha) and examined for MCP-3 protein and mRNA expression using immunocytochemistry and RT-PCR, respectively. RESULTS: In tissue sections, MCP-3 protein was detected predominantly in epithelial cells, both in patients with IBD and in controls. MCP-3 staining was particularly pronounced at sites of active mucosal inflammation. The intensity of MCP-3 staining was positively correlated with the extent of epithelial destruction. In intestinal epithelial cell lines, MCP-3 mRNA was expressed, whereas MCP-3 protein was not consistently detected. CONCLUSIONS: Our data show that MCP-3 protein is present in normal and inflamed intestinal tissue. MCP-3 production is substantially enhanced in areas of active inflammation, suggesting an immunoregulatory role of MCP-3 in intestinal inflammation.

Adult↗
PubMed1998

Circadian elevation of IL-6 levels in Muckle-Wells syndrome: a disorder of the neuro-immune axis?

Muckle-Wells syndrome (MWS) is a rare autosomal dominant hereditary disorder characterized by chronic recurrent urticaria, arthralgia, sensorineural deafness, and in some cases nephropathy due to amyloidosis (AA type). We report a 21-year-old woman and her father, both suffering from this syndrome, in whom elevated serum levels of IL-6 could be documented during the flares of urticaria, and discuss the relevance of this finding for MWS.

Acute Disease↗
PubMed1997

High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines.

Eosinophil leukocytes express high numbers of the chemokine receptor CCR3 which binds eotaxin, monocyte chemotactic protein (MCP)-4, and some other CC chemokines. In this paper we show that CCR3 is also highly expressed on human blood basophils, as indicated by Northern blotting and flow cytometry, and mediates mainly chemotaxis. Eotaxin and MCP-4 elicited basophil migration in vitro with similar efficacy as regulated upon activation normal T cells expressed and secreted (RANTES) and MCP-3. They also induced the release of histamine and leukotrienes in IL-3-primed basophils, but their efficacy was lower than that of MCP-1 and MCP-3, which were the most potent stimuli of exocytosis. Pretreatment of the basophils with a CCR3-blocking antibody abrogated the migration induced by eotaxin, RANTES, and by low to optimal concentrations of MCP-4, but decreased only minimally the response to MCP-3. The CCR3-blocking antibody also affected exocytosis: it abrogated histamine and leukotriene release induced by eotaxin, and partially inhibited the response to RANTES and MCP-4. In contrast, the antibody did not affect the responses induced by MCP-1, MCP-3, and macrophage inflammatory protein-1alpha, which may depend on CCR1 and CCR2, two additional receptors detected by Northern blotting with basophil RNA. This study demonstrates that CCR3 is the major receptor for eotaxin, RANTES, and MCP-4 in human basophils, and suggests that basophils and eosinophils, which are the characteristic effector cells of allergic inflammation, depend largely on CCR3 for migration towards different chemokines into inflamed tissues.

Basophils↗
PubMed1997

Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor CCR3, and acts like eotaxin on human eosinophil and basophil leukocytes.

A novel human CC chemokine consisting of 78 amino acids and having a molecular mass of 8,778.3 daltons (VVIPSPCCMF FVSKRIPENR VVSYQLSSRS TCLKAGVIFT TKKGQQ SCGD PKQEWVQRYM KNLDAKQKKA SPRARAVA) was isolated together with three minor COOH-terminally truncated variants with 73, 75, and 76 residues. The new chemokine was termed eotaxin-2 because it is functionally very similar to eotaxin. In terms of structure, however, eotaxin and eotaxin-2 are rather distant, they share only 39% identical amino acids and differ almost completely in the NH2-terminal region. Eotaxin-2 induced chemotaxis of eosinophils as well as basophils, with a typically bimodal concentration dependence, and the release of histamine and leukotriene C4 from basophils that had been primed with IL-3. In all assays, eotaxin-2 had the same efficacy as eotaxin, but was somewhat less potent. The migration and the release responses were abrogated in the presence of a monoclonal antibody that selectively blocks the eotaxin receptor, CCR3, indicating that eotaxin-2, like eotaxin, acts exclusively via CCR3. Receptor usage was also studied in desensitization experiments by measuring [Ca2+]i changes in eosinophils. Complete cross-desensitization was observed between eotaxin-2, eotaxin and MCP-4 confirming activation via CCR3. No Ca2+ mobilization was obtained in neutrophils, monocytes and lymphocytes, in agreement with the lack of chemotactic responsiveness. Intradermal injection of eotaxin-2 in a rhesus monkey (100 or 1,000 pmol per site) induced a marked local infiltration of eosinophils, which was most pronounced in the vicinity of postcapillary venules and was comparable to the effect of eotaxin.

Amino Acid Sequence↗
PubMed1996

Basophil priming by neurotrophic factors. Activation through the trk receptor.

There is increasing evidence that nerve growth factor (NGF) acts on cells of the immune system, apart from its neurotrophic effects. In human basophils, NGF potentiates mediator release and primes the cells to produce leukotriene C4 in response to C5a. It is, however, unknown whether other homologous neurotrophins also act outside the nervous system, and whether activation of basophils by NGF requires interaction with trk tyrosine kinase receptors, the low affinity NGF receptor (LNGFR), or both. A triple mutant NGF designed to interrupt binding to the LNGFR was found to activate basophils with equal efficacy as wild-type NGF, demonstrating that the LNGFR is not necessary. Despite a 10 times lower potency of mutant NGF, no LNGFR expression was detected by FACS analysis. Brain-derived neurotrophic factor, which interacts with trkB, was inactive at concentrations up to 1000 ng/ml (> 30,000-fold lower potency than NGF), while neurotrophin-3, which is thought to interact with trkC, trkB, and more weakly with trk, induced a threshold effect at 300 ng/ml (approximately 10,000-fold lower potency), demonstrating that 1) the LNGFR cannot deliver a direct signal; and 2) basophils do not express functional trkB and trkC receptors. In agreement with the functional data, basophils (in contrast to other granulocyte types) expressed mRNA for trk, but not trkB or trkC, and no or minimal mRNA for LNGFR. These data demonstrate that human blood basophils express functional trk receptors that do not require the participation of LNGFR, and that, among the neurotrophin family, NGF is unique in priming basophils.

Basophils↗
PubMed1996

Human blood basophils produce interleukin-13 in response to IgE-receptor-dependent and -independent activation.

Interleukin-13 (IL-13) is a recently discovered immunoregulatory cytokine. The cellular sources of IL-13 and the regulation of its expression are largely unknown. Here we show that human basophils produce IL-13 in response to IgE-receptor (IgER) crosslinking, IL-3, IL-3 plus C5a, but not C5a alone. Human basophils express IL-13 in a restricted manner since, apart from IL-4, no other cytokines encoded on the cytokine gene cluster (IL-3, IL-5, and granulocyte macrophage-colony-stimulating factor [GM-CSF]), are induced. Highest levels of IL-13 are formed after IgE-independent activation leading to a prolonged secretion of IL-13. The response to IgER-cross-linking is more transient preferentially inducing IL-4, IL-3 is a unique cytokine regulating IL-13 production by human basophils: Among a large number of cytokines tested, only IL-3 is capable of directly inducing IL-13 expression. Furthermore, although some IL-13 is produced in response to C5a in the presence of IL-5, GM-CSF, IGF-1 or IL-1 beta, IL-3 is by far the most effective. IL-13 production was blocked by actinomycin D and cycloheximide and conditions leading to IL-13 release also lead to the induction of IL-13 mRNA. This study supports an important immunoregulatory role of human blood basophils, owing to their capacity to simultaneously express IL-13 and IL-4 in a restricted manner.

Basophils↗
PubMed1996

Deletion of the NH2-terminal residue converts monocyte chemotactic protein 1 from an activator of basophil mediator release to an eosinophil chemoattractant.

Chemotactic cytokines of the CC subfamily (CC chemokines) are considered as major mediators of allergic inflammation owing their actions on basophil and eosinophil leukocytes. The monocyte chemotactic protein (MCP) 1 is a potent inducer of mediator release from basophils but is inactive on eosinophils. To obtain information on the structural determinants of the activities of MCP-1, we have synthesized several NH2-terminally truncated analogues and tested their effects on basophils and eosinophils. Through deletion of the NH2-terminal residue, MCP-1(2-76) was obtained, which was a potent activator of eosinophils, as assessed by chemotaxis, cytosolic free Ca2+ changes, actin polymerization, and that induction of the respiratory burst. In contrast, the activity of MCP-1(2-76) on basophil leukocytes was dramatically decreased (50-fold) compared with that of full-length MCP-1. Deletion of the next residue led to total loss of activity on eosinophil and basophil leukocytes. Analogues with three or four residue deletions, MCP-1(4-76) and MCP-1(5-76), were again active on both cells, whereas all further truncation analogues, MCP-1(6-76) through MCP-1(10-76), were inactive. Thus, a minimal structural modification can change receptor and target cell selectivity of MCP-1. Our observations indicate that the recognition sites of CC chemokine receptors on eosinophils and basophils are similar, although they discriminate between MCP-1 and MCP-1(2-76) and suggest NH2-terminal processing as a potential mechanism for the regulation of CC chemokine activities.

Actins↗
PubMed1996

Expression of high- and low-affinity receptors for C3a on the human mast cell line, HMC-1.

The proteolytic cleavage product of complement component 3, (C3a), is like C4a and C5a, is a potent anaphylatoxin and induces the production of inflammatory mediators in phagocytes. Notably, mast cells respond to C3a with the release of vasoactive substances, including histamine. We have examined the function and receptor binding of C3a in a human leukemic mast cell line, HMC-1. Similar to chemoattractant agonists in leukocytes, C3a induced rapid cytosolic free calcium concentration increases in HMC-1 cells. EGTA did not diminish this response, indicating that mobilizable Ca2+ was from intracellular stores. Receptors of C3a in HMC-1 cells couple in part to Bordetella pertussis toxin-sensitive G-proteins and, therefore, appear to belong to the family of serpentine receptors that require G-proteins for signal transduction. HMC-1 cells express two types of C3a receptors, C3aR1 and C3aR2, that were shown to bind 125I-C3a with high-(Kd1 = 2.1-4.8 nM) or low-affinity (Kd2 = 30-150 nM), and both receptors are expressed at high level: 3 x 10(5)-6 x 10(5) C3aR1/cell and 5 x 10(5)-2.3 x 10(6) C3aR2/cell. Results from cross-linking experiments with 125I-C3a fully agree with the presence of two different classes of C3a receptors in HMC-1 cells. Two membrane proteins with apparent molecular masses of 54-61 kDa (p57) and 86-107 kDa (p97) could be covalently modified with 125I-C3a, and this cross-linking was inhibited with an excess of unlabeled C3a. Many of the known agonists for leukocytes including 13 chemokines (IL-8, NAP-2, GRO alpha, ENA-78, IP10, PF4, MCP-1, 2 and 3, RANTES, MIP-1 alpha, MIP-1 beta and I309), three neuropeptides (neuropeptide Y, somatostatin and calcitonin), as well as C5a, did not activate HMC-1 cells, indicating that C3a is one of a few protein ligands for which this cell line expresses specific receptors. The apparent selectivity for C3a and the abundant expression of C3a receptors make the HMC-1 cell line an excellent choice for the cloning of the receptor genes.

Anaphylatoxins↗
PubMed1996

Human basophils release interleukin-4 after stimulation with Schistosoma mansoni egg antigen.

The elevated interleukin (IL)-4 and IgE production in Schistosoma mansoni infection seems to be induced essentially by the egg stage of the parasite. The underlying mechanism, however, is not known. Since basophils from human peripheral blood can produce IL-4, we asked, whether soluble S. mansoni egg antigens (SEA) would trigger basophils to release IL-4. Basophils from healthy human donors (n = 32) without prior history of schistosomiasis were incubated with SEA in the presence of IL-3. In all donors, IL-4 was produced at different concentrations. The IL-4 production was dependent on the dose of SEA, was correlated with the purity of the basophil preparation, and the IL-4 concentration in the culture supernatant was maximal 5 h after stimulation with SEA. In addition to its IL-4-stimulatory effect, SEA triggered basophils to degranulate, thereby releasing histamine and sulfidoleukotrienes. Stripping of receptor-bound IgE from basophils inhibited both SEA- and anti-IgE-induced, but not ionomycin-induced IL-4 production. Moreover, resensitization of stripped basophils with stripping supernatants or human serum restored SEA-induced IL-4 production. This suggests that IgE is involved in the mechanism of IL-4 induction by SEA. Since IL-4 is induced in basophils from nonexposed donors, basophils may play a role as an early source of IL-4 in S. mansoni infection.

Animals↗
PubMed1996

Basophil histamine release and leukotriene production in response to anti-IgE and anti-IgE receptor antibodies. Comparison of normal subjects and patients with urticaria, atopic dermatitis or bronchial asthma.

The IgE receptor-dependent in vitro mediator release in basophils is characterized by a large interindividual variability both in normal and atopic subjects. The mechanism and the clinical impact of this finding, however, is largely unclear. The aim of the present study was to examine the role of surface-bound IgE and of response-modifying cytokines such as interleukin 3 (IL-3) as possible factors determining basophil releasability in atopic patients and normal controls. Cells from 30 individuals (6 with urticaria, 7 with asthma, 7 with atopic dermatitis, and 30 healthy controls) were isolated and stimulated for mediator release by IL-3 and different triggering antibodies directed against IgE or IgE receptor. Our data suggest that serum IgE levels and basophil receptor occupancy with IgE are not involved in the mechanism of basophil releasability. Furthermore, IL-3-induced similar effects on mediator release in almost all individuals, rather excluding the possibility that releasability is regulated by cytokine priming of basophils. Interestingly, we found that patients with atopic disease have a reduced capacity of releasing mediators upon activation, the mechanism of which is unclear. In conclusion, our findings support the hypothesis that basophil releasability is dependent on cell-imminent mechanisms in basophils, which may be altered in selected atopic patients.

Adult↗
PubMed1995

IgE-independent interleukin-4 expression and induction of a late phase of leukotriene C4 formation in human blood basophils.

T-helper cells can differentiate into at least two subtypes secreting distinct profiles of cytokines, Th1 and Th2, regulating immunoprotection and different immunopathologies. Interleukin-4 (IL-4) is both the product and the inducer of Th2 cells, raising the question whether IL-4 can be produced in response to antigen-independent stimuli. Here we show that human basophils produce IL-4 on stimulation with IL-3 and C5a or C5adesarg in similar amounts as induced by IgE-receptor-cross-linking. C5a-induced IL-4 production requires the presence of IL-3, with little effect of the sequence of stimuli addition. No "Th1-cytokines" (interferon-gamma and IL-2) and even no "Th2-cytokines" (IL-3, IL-5, IL-10, and granulocyte-macrophage colony-stimulating factor) are produced by basophils in response to either IgE-dependent or IgE-independent activation. The generation of leukotriene C4 (LTC4) is regulated in a similar manner. However, C5a induces a rapid, transient burst of leukotriene formation only if added after IL-3. Interestingly, upon prolonged culture, a late phase of continuous LTC4 production is observed, which also requires two signals (IL-3 and C5a), but rather depends on their continuous presence than on their sequence of action. These data describe an antigen-independent pathway of very restricted IL-4 expression. Thus, basophils must be considered as central immunoregulatory cells of the innate immune system. Furthermore, the results show that LTC4 can also be generated more continuously for many hours, a phenomenon that may be of particular importance in chornic allergic inflammation, such as asthma.

Basophils↗
PubMed1995

Monocyte chemotactic protein MCP-2 activates human basophil and eosinophil leukocytes similar to MCP-3.

It has been shown that CC chemokines activate basophil and eosinophil leukocytes with different selectivities and patterns of activity. The most effective are monocyte chemotactic protein-1 (MCP-1), a potent stimulus of mediator release in basophils without effects on eosinophils, RANTES, a weak stimulus of release and strong chemoattractant for basophils and eosinophils, and MCP-3, which combines the activities of MCP-1 and RANTES. We have now compared MCP-2, which has 62 and 60% of sequence identity with MCP-1 and MCP-3, respectively, with the other CC chemokines. MCP-2 induced mediator release by human basophils with lower efficacy and potency than MCP-1 and MCP-3. It promoted transient changes of cytosolic-free calcium concentration ([Ca2+]i) and chemotactic responses in both basophils and eosinophils, however somewhat less efficiently than MCP-3 and RANTES. Desensitization studies indicate that MCP-2 interacts with receptors recognizing MCP-1 as well as RANTES. These results demonstrate that MCP-2 and MCP-3 exert qualitatively similar biologic activities on basophils and eosinophils. In basophils that had not been treated with IL-3, MCP-2 induced minimal exocytosis only, but desensitized the cells toward MCP-1 and MCP-3, suggesting that MCP-2 may act as a functional inhibitor of CC chemokine actions. The results of this study further indicate that MCP analogues display partially distinct, partially overlapping bioactivities toward eosinophils and basophils, and may thus regulate inflammatory processes involving these effector cell types.

Basophils↗
PubMed1995

Nerve growth factor from the venom of the Chinese cobra Naja naja atra: purification and description of non-neuronal activities.

Nerve growth factor (NGF) was separated from crude Naja naja atra venom by using weak cation-exchange chromatography, followed by reversed-phase liquid chromatography. The yield of the purification was 0.2-0.5% (w/w). The mol. wt was determined to be 13,600 and the protein still induced the typical fibre outgrowth of cultured PC-12 cells in a concentration range of 5-10 ng/ml. Beside this neuronal effect we demonstrated non-neuronal effects of cobra venom NGF, such as induction of plasma extravasation and histamine release from whole blood cells. With human leucocyte preparations, including enriched basophils, there was an increase in C5a-induced histamine release, whereas NGF alone was inactive. Cobra NGF was one-tenth as potent as human recombinant NGF, with a half-maximal stimulation occurring at 10 ng/ml. Cobra NGF and human recombinant NGF showed a modulatory effect on histamine release comparable to the haematopoietic growth factor IL-3. Thus, the non-neuronal effects of cobra NGF may account for immunomodulatory activities during inflammatory events.

Animals↗
PubMed1995

Effects of physiologic soluble agonists on leukotriene C4 production and degranulation by human eosinophils.

The capacities of physiologic soluble agonists to induce leukotriene C4 (LTC4) formation and eosinophil cationic protein release from normal human eosinophils were studied. The most effective stimulus for LTC4 production by eosinophils was N-formyl-methionyl-leucyl-phenylalanine, while that for eosinophil cationic protein release was complement factor 5a. Interleukin-3 (IL-3) and IL-5 modulated both LTC4 formation and eosinophil cationic protein release induced by soluble agonists in a similar fashion, whereas tumor necrosis factor and nerve growth factor affected only LTC4 production. The optimal preincubation period for priming of LTC4 production by IL-3 or IL-5 was 90 min, while that for eosinophil cationic protein release was 10 min. These results indicate that degranulation and the generation of lipid mediators are separately regulated cellular responses, and priming by cytokines may qualitatively change the pathophysiologic consequences of eosinophil activation by soluble agonists.

Blood Proteins↗
PubMed1994

Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine.

CC chemokines constitute a novel class of cytokines that attract and activate monocytes and lymphocytes, as well as basophil and eosinophil leukocytes, with distinct target cell profiles, and are believed to be involved in the regulation of different types of inflammation. The action of the recently identified monocyte chemotactic protein 3 (MCP-3) on human basophil and eosinophil function was studied and compared with that of other CC chemokines. In basophils, MCP-3, MCP-1, RANTES, and macrophage inflammatory protein (MIP)-1 alpha all induced cytosolic-free calcium concentration ([Ca2+]i) changes and, with different efficacies, chemotaxis (RANTES = MCP-3 >> MCP-1 > MIP-1 alpha), histamine release (MCP-1 = MCP-3 >> RANTES > MIP-1 alpha), and leukotriene C4 formation, after IL-3 pretreatment (MCP-1 = MCP-3 >> RANTES > MIP-1 alpha). Thus, MCP-3 was as effective as MCP-1 as an inducer of mediator release, and as effective as RANTES as a stimulus of basophil migration. In contrast to MCP-1, MCP-3 was also a stimulus for eosinophils, and induced [Ca2+]i changes and chemotaxis as effectively as RANTES, which is the most potent chemotactic cytokine for these cells. Desensitization of the transient changes in [Ca2+]i was used to assess receptor usage. In basophils, stimulation with MCP-3 prevented responsiveness to MCP-1 and RANTES, but not to MIP-1 alpha. No single CC chemokine (except for MCP-3 itself) affected the response to MCP-3, however, which was prevented only when the cells were prestimulated with both MCP-1 and RANTES. In eosinophils, by contrast, cross-desensitization between RANTES and MCP-3 was obtained. RANTES and to a lesser extent MCP-3 also desensitized eosinophils toward MIP-1 alpha. The desensitization data suggest the existence of three chemokine receptors: (a) a MCP-1 receptor expressed on basophils but not eosinophils that is activated by MCP-1 and MCP-3; (b) a RANTES receptor in basophils and eosinophils that is activated by RANTES and MCP-3; and (c) a MIP-1 alpha receptor that is activated by MIP-1 alpha, RANTES and, more weakly, by MCP-3. This study shows that MCP-3 combines the properties of RANTES, a powerful chemoattractant, and MCP-1, a highly effective stimulus of mediator release, and thus has a particularly broad range of activities toward both human basophil and eosinophil leukocytes.

Basophils↗
PubMed1994

The degradation product of the C5a anaphylatoxin C5adesarg retains basophil-activating properties.

The complement cleavage product C5a is a potent agonist of different leukocyte types and also has anaphylatoxic properties through the release of mediators by basophils and tissue mast cells. C5a is very rapidly degraded by serum carboxypeptidase N which cleaves the functionally important carboxy-terminal arginine, generating C5desarg, a chemotactic agonist with little mast cell-activating ability. Here we show that natural human C5adesarg is still a trigger for basophil mediator release superior to other endogenous IgE-independent agonists such as monocyte chemotactic protein (MCP)-1, interleukin (IL)-8, C3a and platelet-activating factor. On a molar basis C5adesarg is only one order of magnitude less potent and about half as efficacious as C5a at inducing basophil degranulation. Priming of basophils with either IL-3, IL-5, granulocyte-macrophage-colony-stimulating factor (GM-CSF) or nerve growth factor (NGF) (with comparable efficacies, but different potencies: IL-3 > NGF > IL-5 > GM-CSF) enhanced histamine release and conditioned the cells to produce large amounts of leukotriene C4 (LTC4), which is not generated by basophils exposed to C5adesarg alone. The efficacy of C5a and C5adesarg at inducing histamine and LTC4 release by primed basophils was similar. Thus, C5adesarg is a stable inducer of release of inflammatory mediators by human basophils, particularly in primed cells, and complement may, therefore, play a role in immediate-type hypersensitivity diseases in allergic late-phase reactions.

Basophils↗