Model for Leukocyte Regulation by Chemoattractant Receptors: Roles of a Guanine Nucleotide Regulatory Protein and Polyphosphoinositide Metabolism

Snyderman, Ralph; Smith, Charles D.; Verghese, Margrith W.

doi:10.1002/jlb.40.6.785

Cited by 176 publications

(52 citation statements)

References 89 publications

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“…CXCR2 bound both IL-8 (K d ϭ 2.4 Ϯ 1.3 nM; B max ϭ 8460 Ϯ 232 receptors/cell) and GRO␣ (K d ϭ 1.9 Ϯ 0.9 nM; B max ϭ 7895 Ϯ 637 receptors/cell) with similar affinities. The K d were similar to that of CXCR2 expressed in 3ASubE cells (3.1 nM) (10), HEK 293 cells (4 nM) (21) or the native receptors in neutrophils (ϳ1-2 nM) (26). Upon IL-8 ( Fig.…”

Section: Resultssupporting

confidence: 60%

Differential Cross-regulation of the Human Chemokine Receptors CXCR1 and CXCR2

Richardson¹,

Pridgen²,

Haribabu³

et al. 1998

Journal of Biological Chemistry

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160

179

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Neutrophils and transfected RBL-2H3 cells were used to investigate the mechanism of cross-regulation of the human interleukin-8 (IL-8) receptors CXCR1 and CXCR2 by chemoattractants. In neutrophils, Ca 2؉ mobilization by the CXCR2-specific chemokine, growth-related oncogene ␣ (Gro␣), was desensitized by prior exposure to the chemoattractants N-formylated peptides (fMLP) or a complement cleavage product (C5a). In contrast, growth-related oncogene ␣ did not desensitize the latter receptors. To investigate this phenomenon, CXCR2 was stably expressed in RBL-2H3 cells and mediated phosphoinositide hydrolysis, Ca 2؉ mobilization, chemotaxis, and secretion. In cells co-expressing CXCR2 and receptors for either C5a (C5aR) or fMLP (FR), CXCR2 was cross-phosphorylated and cross-desensitized by C5a and fMLP. However, neither C5aR nor FR was cross-phosphorylated or cross-desensitized by CXCR2 activation, although CXCR1 did mediate this process. Receptor internalization induced by IL-8 was more rapid and occurred at lower doses with CXCR2 than CXCR1, although both receptors mediated equipotent chemotaxis and exocytosis in RBL. Truncation of the cytoplasmic tail of CXCR2 (331T) prolonged its signaling relative to CXCR2, increased its resistance to internalization, and induced phospholipase D activation. 331T was resistant to homologous phosphorylation and cross-phosphorylation but not cross-desensitization of its Ca 2؉ mobilization by fMLP or C5a, indicating an inhibitory site distal to receptor/G protein coupling. In contrast to CXCR2, stimulation of 331T cross-desensitized Ca 2؉ mobilization by both FR and C5aR. CXCR2 and the mutant 331T induced phospholipase C ␤ 3 phosphorylation to an extent equivalent to that of CXCR1. Taken together, these results suggest that CXCR1 and CXCR2 bind IL-8 to produce a group of equipotent responses, but their ability to generate other signals, including receptor internalization, cross-desensitization, and phospholipase D activation, are very different. The latter phenomena apparently require prolonged receptor activation, which in the case of CXCR2 is precluded by rapid receptor phosphorylation and internalization. Thus, receptors coupling to identical G proteins may trigger different cellular responses dependent on the length of their signaling time, which can be regulated by receptor phosphorylation.

show abstract

Section: Resultssupporting

confidence: 60%

Differential Cross-regulation of the Human Chemokine Receptors CXCR1 and CXCR2

Richardson¹,

Pridgen²,

Haribabu³

et al. 1998

Journal of Biological Chemistry

Self Cite

160

179

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show abstract

“…A mechanism involving both membrane potential and short range diffusion might account for these observations. One likely participant is inositol 1,4,5-triphosphate, which is generated during FMLP stimulation of neutrophils (54). Inositol 1,4,5-triphosphate promotes Ca 2ϩ release from the ER, which in turn triggers store-operated Ca 2ϩ influx across the plasma membrane (55).…”

Section: Discussionmentioning

confidence: 99%

Intracellular Calcium Waves Accompany Neutrophil Polarization, Formylmethionylleucylphenylalanine Stimulation, and Phagocytosis: A High Speed Microscopy Study

Kindzelskii

Petty

2003

The Journal of Immunology

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Using high sensitivity fluorescence imaging with shutter speeds ∼600,000 times faster than those of video frames, we have characterized Ca2+ waves within cells in exquisite detail to reveal Ca2+ signaling routes. Polarized neutrophils exhibited a counterclockwise rotating ryanodine-sensitive juxtamembrane Ca2+ wave during temporal calcium spikes. During stimulation with fMLP, a chemotactic factor, two Ca2+ waves traveling in opposite directions around the perimeter of the cell emanated from sites of stimulation (the clockwise wave is verapamil sensitive). Phagocytosed targets exhibit counterclockwise Ca2+ waves traveling about their periphery originating from the plasma membrane. This study: 1) outlines the technology to observe Ca2+ signaling circuitry within small living cells; 2) shows that extracellular spatial information in the form of a chemotactic factor gradient is transduced into intracellular chemical patterns, which provides fresh insights in signaling; 3) suggests that a line of communication exits between the cell surface and phagosomes; and 4) suggests that spatiotemporal Ca2+ patterns contribute to drug actions.

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“…We have demonstrated that IGF-I is chemotactic for resting and activated human T lymphocytes with a half-maximal concentration consistent with the Kd of the receptor, providing evidence that the effect shown is mediated via high-affinity IGF-I receptors. In addition, the gradient-enhanced motility (chemotaxis) and high-dose inhibition demonstrated resemble that seen with insulin (20), , and with other receptor-mediated chemotaxis models such as N-formylated-methionyl peptides for neutrophils (36,37) and platelet-derived growth factor for neutrophils and monocytes (38,39). However, the precise mechanism through which IGF-I enhances T cell motility is unclear.…”

Section: Discussionmentioning

confidence: 92%

Structural and functional characterization of the human T lymphocyte receptor for insulin-like growth factor I in vitro.

Tapson

Böni-Schnetzler²,

Pilch³

et al. 1988

J. Clin. Invest.

119

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Growth factor receptors for T lymphocytes, such as interleukin 2 and insulin, are present on activated but not resting T lymphocytes. We sought to determine if insulin-like growth factor I (IGF-I) could act as a growth factor for human T cells and to characterize its receptor on resting and activated cells. Recombinant IGF-I induced two separate functions. It was chemotactic for and increased incorporation of tritiated thymidine into both unactivated (resting) and mitogen-activated T cells.

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Model for Leukocyte Regulation by Chemoattractant Receptors: Roles of a Guanine Nucleotide Regulatory Protein and Polyphosphoinositide Metabolism

Cited by 176 publications

References 89 publications

Differential Cross-regulation of the Human Chemokine Receptors CXCR1 and CXCR2

Differential Cross-regulation of the Human Chemokine Receptors CXCR1 and CXCR2

Intracellular Calcium Waves Accompany Neutrophil Polarization, Formylmethionylleucylphenylalanine Stimulation, and Phagocytosis: A High Speed Microscopy Study

Structural and functional characterization of the human T lymphocyte receptor for insulin-like growth factor I in vitro.

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