The oligopeptide chemotactic factor receptor on human polymorphonuclear leukocyte membranes exists in two affinity states

Koo, Catherine H.; Lefkowitz, Robert J.; Snyderman, Ralph

doi:10.1016/0006-291x(82)91130-5

Cited by 141 publications

(53 citation statements)

References 12 publications

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“…Results were best represented by curvilinear lines (Fig. 3), consistent with the presence of high and low affinity receptors (17). Normal PMN exhibited 45,586±4,818 high affinity receptors (Kd 0.43±0.25 nM) and 127,387±2,790 low affinity receptors (Kd 2.95± 1.1 nM) per cell (mean±SE, n = 3).…”

Section: Resultssupporting

confidence: 65%

Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile periodontitis.

Perez

Kelly²,

Elfman

et al. 1991

J. Clin. Invest.

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Section: Resultssupporting

confidence: 65%

Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile periodontitis.

Perez

Kelly²,

Elfman

et al. 1991

J. Clin. Invest.

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“…For example, 50,000 -120,000 FR are present on neutrophils (17,18). In contrast, C3aR expression in monocytes, neutrophils, eosinophils, and basophils ranges from 3,000 to 10,000 copies/cell (22).…”

Section: Discussionmentioning

confidence: 99%

“…The transfectants were analyzed for their ability to bind [ 3 H]fMLP and to mobilize Ca 2ϩ in response to fMLP. Saturation binding studies revealed the presence of 54,354 Ϯ 3,478 binding sites/cell, which compares to 55,000 -120,000 binding sites for natively expressed receptors in human neutrophils (17,18). As shown in Fig.…”

Section: Characterization Of Expressed Ha-fr In Hmc-1 Cellsmentioning

confidence: 95%

Chemokine Production by G Protein-Coupled Receptor Activation in a Human Mast Cell Line: Roles of Extracellular Signal-Regulated Kinase and NFAT

Ali

Ahamed

Hernández-Munaín

et al. 2000

The Journal of Immunology

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Chemoattractants are thought to be the first mediators generated at sites of bacterial infection. We hypothesized that signaling through G protein-coupled chemoattractant receptors may stimulate cytokine production. To test this hypothesis, a human mast cell line (HMC-1) that normally expresses receptors for complement components C3a and C5a at low levels was stably transfected to express physiologic levels of fMLP receptors. We found that fMLP, but not C3a or C5a, induced macrophage inflammatory protein (MIP)-1β (CCL4) and monocyte chemoattractant protein-1 (CCL2) mRNA and protein. Although fMLP stimulated both sustained Ca2+ mobilization and phosphorylation of extracellular signal-regulated kinase (ERK), these responses to C3a or C5a were transient. However, transient expression of C3a receptors in HMC-1 cells rendered the cells responsive to C3a for sustained Ca2+ mobilization and MIP-1β production. The fMLP-induced chemokine production was blocked by pertussis toxin, PD98059, and cyclosporin A, which respectively inhibit Giα activation, mitgen-activated protein kinase kinase-mediated ERK phosphorylation, and calcineurin-mediated activation of NFAT. Furthermore, fMLP, but not C5a, stimulated NFAT activation in HMC-1 cells. These data indicate that chemoattractant receptors induce chemokine production in HMC-1 cells with a selectivity that depends on the level of receptor expression, the length of their signaling time, and the synergistic interaction of multiple signaling pathways, including extracellular signal-regulated kinase phosphorylation, sustained Ca2+ mobilization and NFAT activation.

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“…It has been demonstrated that the C5a receptor is derived from a single copy gene (Gerard et al, 1992;Perret et al, 1992), thus arguing against the existence of multiple C5a receptor isotypes of varying affinity on different cell types within a species. Alternatively, cell type-specific cellular factors that influence ligand affinity and/or the activation state of rhodopsin family receptors including G protein-receptor interactions, signal messengers, and receptor kinases (Koo et al, 1982;Didsbury et al, 1991) could in part account for differences observed in apparent C5a potency observed in various biological assays.…”

Section: Io" Io-'mentioning

confidence: 99%

Primary structure and functional characterization of rat C5a: An anaphylatoxin with unusually high potency

1994

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The anaphylatoxin C5a is a pro-inflammatory factor generated from C5 during complement activation. C5a derived from rat C5 exhibits significantly greater potency compared to C5a from other species. Rat C5a was 25-fold more potent than human C5a for eliciting spasmogenic contraction of guinea pig ileum. Proteolytic removal of the C-terminal arginine of C5a (CSadesArg) reduced spasmogenic potency of rat C5a by only 4-fold compared to a 3,000-fold reduction for human CSadesArg. In addition, rat C5qesArg was 50-fold more potent than human ChdesArg in a guinea pig vascular permeability (in vivo) assay and as a chemotactic factor for human neutrophils. C5a and C5qesArg were purified from zymosan-activated rat serum. Rat C5a, like human C5a, is glycosylated but contains 77 amino acid residues instead of the 74 residues of human C5a. Comparison of the primary structures of rat and human C5a indicated differences at 30 positions including an insert of 3 residues (LLH) in the rat molecule between residue positions 3 and 4 in human C5a. Insertion of residues LLH between Gln-3 and Lys-4 in a recombinant human C5a molecule using site-directed mutagenesis failed to enhance potency. Synthetic C-terminal analogues of rat C5a proved to be measurably more potent than the corresponding human C5a analogues (Ember JA et al., 1993, Protein Sci Z(Supp1 1):159 [Abstr]). We conclude that multiple sequence differences in the C-terminal effector portion and/or elsewhere in rat C5a, but not the LLH insert, account for the significant enhancement in potency of rat C5a over C5a from other species.Keywords: anaphylatoxin; complement; C5a; rat; spasmogen As early as 1910, Friedberger demonstrated an activity in complement-activated animal sera that when administered intravenously was lethally toxic to guinea pigs (Friedberger, 1910). Because the treated animals appeared to undergo an anaphylactoid shock reaction, the term anaphylatoxin was coined to identify the lethal substance (Friedberger, 1910). Later it was reported that C5a generated in C-activated rat serum exhibited unusually potent in vivo effects in guinea pigs in comparison to C5a derived from other species (Friedberger et al., 1964). In

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The oligopeptide chemotactic factor receptor on human polymorphonuclear leukocyte membranes exists in two affinity states

Cited by 141 publications

References 12 publications

Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile periodontitis.

Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile periodontitis.

Chemokine Production by G Protein-Coupled Receptor Activation in a Human Mast Cell Line: Roles of Extracellular Signal-Regulated Kinase and NFAT

Primary structure and functional characterization of rat C5a: An anaphylatoxin with unusually high potency

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