CXCR2 stimulation primes CXCR1 [Ca2+]i responses to IL-8 in human neutrophils

Carl J. Hauser, Zoltan Fekete, Elliot R. Goodman, Eric Kleinstein, David Livingston, Edwin A. Deitch

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Neutrophil (PMN) priming and subsequent responses to the IL-8 presented on pulmonary endothelial surfaces may be crucial determinants of the development of adult respiratory distress syndrome after injury. Elevated plasma ELR+ C-X-C chemokine (CXC) levels might contribute to PMN priming after trauma, but the role of CXCs in priming circulating PMNs is unstudied. We evaluated the interactions of IL-8 and GRO-α in priming human PMN calcium fluxes [Ca2+]i within circulatory environments. At physiologic concentrations, GRO-α primes PMN for IL-8 mediated [Ca2+]i mobilization, whereas IL-8 abolishes GRO-α responses. Repeated GRO-α exposures further enhance IL-8 responses. PMN priming for IL-8 responses in normal plasma was CXCR2 dependent. CXCR2 was more responsive than CXCR1 to low levels of IL-8, together suggesting that CXCR2 is the important CXC receptor at circulating (i.e., low) agonist concentrations. CXCR1 stimulation down-regulated CXCR2 surface expression, whereas CXCR2 stimulation upregulated CXCR1 expression. GRO-α / CXCR2 signaling enhanced post-receptor IL-8 initiated PMN [Ca2+]i influx as well as efflux. Sufficient stimulation of the CXCR1 terminated this cooperative relationship by down-regulating surface expression of CXCR2. This study is the first to report that at physiologic concentrations, C-X-C chemokines can act on circulating human PMNs as an integrated system where CXCR2 agonists, rather than cross-desensitizing CXCR1, act to enhance signaling of IL-8 at CXCR1 both by receptor and post-receptor mechanisms. Such CXCR2 mediated priming of CXCR1/ IL-8 interaction may enhance PMN attack on the lung after injury.

Original languageEnglish (US)
Pages (from-to)428-437
Number of pages10
JournalShock
Volume12
Issue number6
DOIs
StatePublished - Jan 1 1999

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Interleukin-8
Neutrophils
CXC Chemokines
Interleukin-8A Receptors
Interleukin-8 Receptors
Chemokine Receptors
Adult Respiratory Distress Syndrome
Wounds and Injuries
Lung Injury
Calcium
Lung

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Hauser, C. J., Fekete, Z., Goodman, E. R., Kleinstein, E., Livingston, D., & Deitch, E. A. (1999). CXCR2 stimulation primes CXCR1 [Ca2+]i responses to IL-8 in human neutrophils. Shock, 12(6), 428-437. https://doi.org/10.1097/00024382-199912000-00003
Hauser, Carl J. ; Fekete, Zoltan ; Goodman, Elliot R. ; Kleinstein, Eric ; Livingston, David ; Deitch, Edwin A. / CXCR2 stimulation primes CXCR1 [Ca2+]i responses to IL-8 in human neutrophils. In: Shock. 1999 ; Vol. 12, No. 6. pp. 428-437.
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abstract = "Neutrophil (PMN) priming and subsequent responses to the IL-8 presented on pulmonary endothelial surfaces may be crucial determinants of the development of adult respiratory distress syndrome after injury. Elevated plasma ELR+ C-X-C chemokine (CXC) levels might contribute to PMN priming after trauma, but the role of CXCs in priming circulating PMNs is unstudied. We evaluated the interactions of IL-8 and GRO-α in priming human PMN calcium fluxes [Ca2+]i within circulatory environments. At physiologic concentrations, GRO-α primes PMN for IL-8 mediated [Ca2+]i mobilization, whereas IL-8 abolishes GRO-α responses. Repeated GRO-α exposures further enhance IL-8 responses. PMN priming for IL-8 responses in normal plasma was CXCR2 dependent. CXCR2 was more responsive than CXCR1 to low levels of IL-8, together suggesting that CXCR2 is the important CXC receptor at circulating (i.e., low) agonist concentrations. CXCR1 stimulation down-regulated CXCR2 surface expression, whereas CXCR2 stimulation upregulated CXCR1 expression. GRO-α / CXCR2 signaling enhanced post-receptor IL-8 initiated PMN [Ca2+]i influx as well as efflux. Sufficient stimulation of the CXCR1 terminated this cooperative relationship by down-regulating surface expression of CXCR2. This study is the first to report that at physiologic concentrations, C-X-C chemokines can act on circulating human PMNs as an integrated system where CXCR2 agonists, rather than cross-desensitizing CXCR1, act to enhance signaling of IL-8 at CXCR1 both by receptor and post-receptor mechanisms. Such CXCR2 mediated priming of CXCR1/ IL-8 interaction may enhance PMN attack on the lung after injury.",
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Hauser, CJ, Fekete, Z, Goodman, ER, Kleinstein, E, Livingston, D & Deitch, EA 1999, 'CXCR2 stimulation primes CXCR1 [Ca2+]i responses to IL-8 in human neutrophils', Shock, vol. 12, no. 6, pp. 428-437. https://doi.org/10.1097/00024382-199912000-00003

CXCR2 stimulation primes CXCR1 [Ca2+]i responses to IL-8 in human neutrophils. / Hauser, Carl J.; Fekete, Zoltan; Goodman, Elliot R.; Kleinstein, Eric; Livingston, David; Deitch, Edwin A.

In: Shock, Vol. 12, No. 6, 01.01.1999, p. 428-437.

Research output: Contribution to journalArticle

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T1 - CXCR2 stimulation primes CXCR1 [Ca2+]i responses to IL-8 in human neutrophils

AU - Hauser, Carl J.

AU - Fekete, Zoltan

AU - Goodman, Elliot R.

AU - Kleinstein, Eric

AU - Livingston, David

AU - Deitch, Edwin A.

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Y1 - 1999/1/1

N2 - Neutrophil (PMN) priming and subsequent responses to the IL-8 presented on pulmonary endothelial surfaces may be crucial determinants of the development of adult respiratory distress syndrome after injury. Elevated plasma ELR+ C-X-C chemokine (CXC) levels might contribute to PMN priming after trauma, but the role of CXCs in priming circulating PMNs is unstudied. We evaluated the interactions of IL-8 and GRO-α in priming human PMN calcium fluxes [Ca2+]i within circulatory environments. At physiologic concentrations, GRO-α primes PMN for IL-8 mediated [Ca2+]i mobilization, whereas IL-8 abolishes GRO-α responses. Repeated GRO-α exposures further enhance IL-8 responses. PMN priming for IL-8 responses in normal plasma was CXCR2 dependent. CXCR2 was more responsive than CXCR1 to low levels of IL-8, together suggesting that CXCR2 is the important CXC receptor at circulating (i.e., low) agonist concentrations. CXCR1 stimulation down-regulated CXCR2 surface expression, whereas CXCR2 stimulation upregulated CXCR1 expression. GRO-α / CXCR2 signaling enhanced post-receptor IL-8 initiated PMN [Ca2+]i influx as well as efflux. Sufficient stimulation of the CXCR1 terminated this cooperative relationship by down-regulating surface expression of CXCR2. This study is the first to report that at physiologic concentrations, C-X-C chemokines can act on circulating human PMNs as an integrated system where CXCR2 agonists, rather than cross-desensitizing CXCR1, act to enhance signaling of IL-8 at CXCR1 both by receptor and post-receptor mechanisms. Such CXCR2 mediated priming of CXCR1/ IL-8 interaction may enhance PMN attack on the lung after injury.

AB - Neutrophil (PMN) priming and subsequent responses to the IL-8 presented on pulmonary endothelial surfaces may be crucial determinants of the development of adult respiratory distress syndrome after injury. Elevated plasma ELR+ C-X-C chemokine (CXC) levels might contribute to PMN priming after trauma, but the role of CXCs in priming circulating PMNs is unstudied. We evaluated the interactions of IL-8 and GRO-α in priming human PMN calcium fluxes [Ca2+]i within circulatory environments. At physiologic concentrations, GRO-α primes PMN for IL-8 mediated [Ca2+]i mobilization, whereas IL-8 abolishes GRO-α responses. Repeated GRO-α exposures further enhance IL-8 responses. PMN priming for IL-8 responses in normal plasma was CXCR2 dependent. CXCR2 was more responsive than CXCR1 to low levels of IL-8, together suggesting that CXCR2 is the important CXC receptor at circulating (i.e., low) agonist concentrations. CXCR1 stimulation down-regulated CXCR2 surface expression, whereas CXCR2 stimulation upregulated CXCR1 expression. GRO-α / CXCR2 signaling enhanced post-receptor IL-8 initiated PMN [Ca2+]i influx as well as efflux. Sufficient stimulation of the CXCR1 terminated this cooperative relationship by down-regulating surface expression of CXCR2. This study is the first to report that at physiologic concentrations, C-X-C chemokines can act on circulating human PMNs as an integrated system where CXCR2 agonists, rather than cross-desensitizing CXCR1, act to enhance signaling of IL-8 at CXCR1 both by receptor and post-receptor mechanisms. Such CXCR2 mediated priming of CXCR1/ IL-8 interaction may enhance PMN attack on the lung after injury.

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