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

When stimulated with immune complex or C5a anaphylatoxin, human neutrophils undergo an increase in the concentration of intracellular Ca2+ [( Ca2+]i) that precedes the onset of superoxide (O2-) production. The extracellular Ca2+ is required for the O2- production of neutrophils stimulated by C5a, but is only partially required for those by immune complex. The addition of pertussis toxin to neutrophils does not inhibit the rise in [Ca2+]i and O2- production induced by immune complex but does inhibit those induced by C5a. These results suggest that a different sequence of reaction is involved by different stimulants, the anaphylatoxin and immune complex.
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PMID:Different sensitivities of the responses of human neutrophils stimulated with immune complex and C5a anaphylatoxin to pertussis toxin. 283 63

Human neuroblastoma TGW cells express a C5a anaphylatoxin receptor-like molecule termed neuronal C5a receptor. A C5a-receptor fragment peptide (termed PR226-multiple antigenic peptide) can induce rapid apoptosis in TGW cells via neuronal C5a receptor-associated signal transduction pathways. In order to analyse role of activated complement system in neurodegeneration, TGW cells were exposed to an oligomer form of a C5a fragment (amino acids: 37-53) peptide termed PL37-multiple antigenic peptide. Upon treatment with PL37-multiple antigenic peptide, an increased nuclear c-fos expression was shown within 30 min. DNA fragmentation, a hallmark of apoptosis, was noted within 4 h. Extracellular administration of 100 nM PL37-multiple antigenic peptide evoked inward calcium current pulses. At higher doses (0.5 microM-1 microM), PL37-multiple antigenic peptide evoked higher current pulses, followed by an irreversible, high inward current. To exert its apoptotic effect, PL37-multiple antigenic peptide utilizes a pertussis toxin-sensitive signal transduction pathway associated with the neuronal C5a receptor. Activation of the complement system and therefore release of C5a has already been reported in Alzheimer's disease. In addition, the presence of the Kunitz-type proteinase inhibitors indicates an impaired protease function and a possible abnormal fragmentation of C5a anaphylatoxin. Our data suggest that neurons expressing neuronal C5a receptor are more vulnerable to the apoptosis associated with the neuronal C5a receptor and the possibility that abnormal activation of C5a receptor and C5a anaphylatoxin fragments might be involved in the pathogenesis of Alzheimer's disease.
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PMID:Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells. 969 26

A recombinant complement anaphylatoxin, C4a, inhibited chemotaxis, respiratory burst and histamine release in mast cell-like HMC-1 cells that were treated with recombinant C5a anaphylatoxin. C4a also inhibited histamine release from HMC-1 cells that were induced by recombinant C3a. The inhibition of C5a- and C3a-induced leukocyte reactions by C4a was recapitulated in peripheral blood CD133(+) cell-derived differentiated mast cells. In HMC-1 cells, C4a inhibited cytoplasmic Ca(2+) influx, an event that precedes anaphylatoxin-induced chemotactic and secretary responses. A conditioned medium of HMC-1 cells after shortly treated with C4a also inhibited the anaphylatoxin-induced Ca(2+) influx even after removal of C4a, indicating that the effect of C4a is to liberate an autocrine inhibitor from the mast cells. The inhibitor secretion by C4a was prevented with pertussis toxin or with a phosphodiesterase inhibitor. Conversely, an adenylyl cyclase inhibitor reproduced the effect of C4a. C4a decreased the intracellular cyclic AMP concentration of HMC-1 cells, indicating that C4a elicited the Gi protein-adenylyl cyclase inhibition pathway. Neither C4a nor the conditioned medium, however, inhibited Ca(2+) influx and respiratory burst in C5a- or C3a-stimulated peripheral neutrophils, suggesting that these cells lack this inhibitory system. Additionally, in HMC-1 cells, C4a did not inhibit Ca(2+)-independent, Leu72Gln-C5a-stimulated chemotactic response. In agreement with this finding, C4a treatment inhibited ERK1/2 phosphorylation in HMC-1 cells stimulated with other anaphylatoxins but did not inhibit p38MAPK phosphorylation in cells stimulated with Leu72Gln-C5a. Taken together, these findings suggest that the autocrine inhibitory effect elicited by C4a is attributed to interruption of Ca(2+)-dependent intracellular signaling pathway.
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PMID:Inhibitory effects of C4a on chemoattractant and secretagogue functions of the other anaphylatoxins via Gi protein-adenylyl cyclase inhibition pathway in mast cells. 2215 25