Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pertussis toxin (PT) was found to elicit an increased thymidine uptake in resting B lymphocytes purified from human peripheral blood. A significant mitogenic effect was detected for toxin concentrations greater than 100 ng/ml (1nM) and a plateau of stimulation was reached at 1000 ng/ml (10 nM). B cell blasts, activated by a first signal such as Staphylococcus aureus Cowan I or insolubilized anti-mu chain antibody, were also stimulated to DNA synthesis by PT in the same range of concentrations. At lower sub-mitogenic concentrations, the toxin potentiated the response to the low-molecular weight B cell growth factor (LMW-BCGF or 12-kDa BCGF), a progression factor for activated B cells. The "A" or catalytic subunit was devoid of any activity on B cells, suggesting the stimulatory effect of the toxin might be associated with the binding or "B" subunit, as it has been shown for T cells. This hypothesis was strengthened by the observation that, as in T cell, the whole toxin but not the "A" promoter, was able to induce calcium influx in these cells. In addition, the purified "B" oligomer alone was found to promote DNA synthesis in B cells. Finally, a fragment of the soluble cleaved form of the CD23 molecule (Fc epsilon RII) could be involved in the process of PT mitogenicity for B cells.
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PMID:Effect of bacterial toxins on human B cell activation. I. Mitogenic activity of pertussis toxin. 214 73

Transduction through the CD23 molecule (Fc epsilon RII) was analyzed in human activated B lymphocytes using anti-CD23 mAb. B cell blasts expressing an increased amount of surface CD23 molecule were obtained by stimulation of normal peripheral blood B lymphocytes with Staphylococcus aureus strain Cowan I and IL-4. Anti-CD23 mAb were found to trigger polyphosphoinositide hydrolysis in these cells (and also in tumoral B cells expressing spontaneously CD23) and a rise in [Ca2+]i which could be attributed to mobilization from cytoplasmic pools. This increase in [Ca2+]i could be mimicked, with a comparable time-course, by the addition of InsP3 to permeabilized B cell blasts indicating that the increase in inositol phosphate accumulation induced by the antibodies was due to a preferential attack of phosphatidylinositol-bisphosphate by a specific phosphoinositidase C (PIC). In permeabilized cells, raising the free calcium concentration above 3 microM was found to induce polyphosphoinositides hydrolysis and to activate directly the PIC. Addition of 100 microM GTP-tetralithium salt, a non-hydrolyzable analogue of GTP, also resulted in an increased accumulation of inositol phosphates. A Ca2(+)-dependent PIC, linked to a GTP-binding protein (Gp protein), can thus be activated in B cell blasts. Addition of anti-CD23 antibodies to permeabilized B cells in the presence of a physiologic concentration of Ca2+ (100 nM) evoked, within 10 min, a rise in the various inositol phosphates. This ability of anti-CD23 antibodies to activate PIC was enhanced in the presence of GTP-tetralithium salt 100 microM. By contrast, preincubation with GDP-trilithium salt, a nonhydrolyzable analogue of GDP, caused a marked reduction in the release of inositol phosphates. Preincubation of B cell blasts with Pertussis toxin resulted in a total inhibition of the capacity of the toxin to ADP-ribosylate a 41-kDa protein, probably of the Gi type; in these conditions, no modification of anti-CD23-elicited polyphosphoinositide hydrolysis could be detected. These results suggest that the CD23 molecule may be coupled to the phosphoinositide signaling pathway by a GTP-dependent component that is insensitive to Pertussis toxin.
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PMID:Monoclonal anti-CD23 antibodies induce a rise in [Ca2+]i and polyphosphoinositide hydrolysis in human activated B cells. Involvement of a Gp protein. 216 62

Ligation of the low affinity IgE receptor by specific monoclonal antibodies or multivalent IgE complexes result in the transduction of signals which differ according to the CD23 isotype expressed by the various cell types. In B lymphocytes, it elicits the early activation of phospholipase C through a mechanism involving a G-protein insensitive to Pertussis toxin, followed by a late phase of cAMP accumulation. In monocytes, which express the CD23b isoform, ligation of CD23 was also found to induce a delayed accumulation of cAMP, that was largely dependent on a prior cGMP increase through a mechanism involving the activation of a NO synthase. This pathway, which appears to be exacerbated in allergic diseases, seems to play an important role in the differentiation of cells of the monocytic lineage, their capacity to release proinflammatory mediators and their cytotoxic functions.
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PMID:[Physiopathological role of low affinity IgE receptor (CD23) in hematopoietic cells]. 752 27

The low affinity IgE receptor CD23 may play a role in several B lymphocyte functions, such as cell activation and multiplication, Ag presentation, and IgE production. We have previously reported that ligation of the CD23 molecule with anti-CD23 mAb, or IgE-anti-IgE complexes, leads to phosphoinositide hydrolysis and calcium mobilization through the generation of Inositol (1,4,5) trisphosphate via a process involving a Pertussis toxin insensitive GTP-binding protein. In our work, we show that anti-CD23 mAb elicit an increase in cAMP concentration in human peripheral blood-derived B lymphocytes. This effect was detected both in resting and in IL-4-stimulated B cells displaying, respectively, low and high levels of CD23. Maximum cAMP accumulation was reached about 20 min after addition of the mAb. Involvement of Fc gamma RII in this process could be excluded because cAMP increase was also triggered by mAb anti-CD23 F(ab')2 fragments. Accumulation of cAMP was also observed when IgE-sensitized activated B lymphocytes were challenged with the specific hapten. Several lines of evidence indicate that the cAMP increase after CD23 ligation may result, in part, from the stimulation of phosphoinositidase C, inasmuch as it was markedly impaired by treatment with TMB-8, an inhibitor of InsP3-induced calcium release from intracytoplasmic stores and with BAPTA, an intracellular calcium chelator. Addition of GTP-gamma S to permeabilized B cells or to membrane preparations did not potentiate the effect of the mAb, suggesting that a Gs protein is not directly implicated in the generation of cAMP. Besides, cAMP accumulation is not due to the production of PG because it is not modified by indomethacin, an inhibitor of the cyclooxygenase pathway. Pretreatment of B lymphocytes with either anti-CD23 mAb or IL-4 led to autologous as well as heterologous desensitization. This negative cross-talk, at the level of cAMP, between the signaling pathways triggered by ligation of CD23 and of the IL-4 receptor, could contribute to the inhibitory effect of anti-CD23 mAb on IL-4-dependent B cell activation and differentiation.
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PMID:Ligation of CD23 triggers cyclic AMP generation in human B lymphocytes. 838 20

African trypanosomes of the Trypanosoma brucei species are extra-cellular parasites that cause human African trypanosomiasis (HAT) as well as infections in game animals and livestock. Trypanosomes are known to evade the immune response of their mammalian host by continuous antigenic variation of their surface coat. Here, we aim to demonstrate that in addition, trypanosomes (i) cause the loss of various B cell populations, (ii) disable the hosts' capacity to raise a long-lasting specific protective anti-parasite antibody response, and (iii) abrogate vaccine-induced protective response to a non-related human pathogen such as Bordetella pertussis. Using a mouse model for T. brucei, various B cell populations were analyzed by FACS at different time points of infection. The results show that during early onset of a T. brucei infection, spleen remodeling results in the rapid loss of the IgM(+) marginal zone (IgM(+)MZ) B cell population characterized as B220(+)IgM(High)IgD(Int) CD21(High)CD23(Low)CD1d(+)CD138(-). These cells, when isolated during the first peak of infection, stained positive for Annexin V and had increased caspase-3 enzyme activity. Elevated caspase-3 mRNA levels coincided with decreased mRNA levels of the anti-apoptotic Bcl-2 protein and BAFF receptor (BAFF-R), indicating the onset of apoptosis. Moreover, affected B cells became unresponsive to stimulation by BCR cross-linking with anti-IgM Fab fragments. In vivo, infection-induced loss of IgM(+) B cells coincided with the disappearance of protective variant-specific T-independent IgM responses, rendering the host rapidly susceptible to re-challenge with previously encountered parasites. Finally, using the well-established human diphtheria, tetanus, and B. pertussis (DTPa) vaccination model in mice, we show that T. brucei infections abrogate vaccine-induced protective responses to a non-related pathogen such as B. pertussis. Infections with T. brucei parasites result in the rapid loss of T-cell independent IgM(+)MZ B cells that are normally functioning as the primary immune barrier against blood-borne pathogens. In addition, ongoing trypanosome infections results in the rapid loss of B cell responsiveness and prevent the induction of protective memory responses. Finally, trypanosome infections disable the host's capacity to recall vaccine-induced memory responses against non-related pathogens. In particular, these last results call for detailed studies of the effect of HAT on memory recall responses in humans, prior to the planning of any mass vaccination campaign in HAT endemic areas.
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PMID:Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses. 1851

Mast cells are bone marrow-derived effector cells that can initiate inflammatory responses to infectious organisms or allergens by releasing a multitude of pro-inflammatory factors including prostaglandin (PG) D(2). We demonstrate that primary murine bone marrow-derived mast cells (BMMCs) express the PGD(2) receptor; chemoattractant receptor-homologous molecule expressed on T(h) class 2 cells (CRT(h)2). Activation of CRT(h)2 on BMMC by PGD(2) or the CRT(h)2-specific agonist, 13,14-dihydro-15-keto-prostaglandin D(2) (DK-PGD(2)), resulted in signaling response including Ca(2+) mobilization and phosphorylation of the p42/p44 extracellular signal-regulated kinases (ERKs) kinases. Phosphorylation of the ERKs could be blocked by pertussis toxin, as well as a small molecule antagonist of CRT(h)2, Compound A. Activation of CRT(h)2 on BMMC also resulted in the up-regulation of CD23 and CD30 on the cell surface, as well as CD62L shedding. Finally, PGD(2) and DK-PGD(2) induced the migration of BMMC in vitro and in vivo in response to an intra-dermal DK-PGD(2) injection. Both these processes were inhibited by the CRT(h)2 antagonist. These results raise the possibility that the functional consequences of the PGD(2)-CRT(h)2 interaction on mast cells may be relevant in allergic inflammation.
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PMID:Murine bone marrow-derived mast cells express chemoattractant receptor-homologous molecule expressed on T-helper class 2 cells (CRTh2). 1934 59