Monomeric and dimeric CXCL8 are both essential for in vivo neutrophil recruitment

Sandhya Thulasi Das, Lavanya Rajagopalan, Antonieta Guerrero-Plata, Jiqing Sai, Ann Richmond, Roberto Garofalo, Krishna Rajarathnam

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Rapid mobilization of neutrophils from vasculature to the site of bacterial/viral infections and tissue injury is a critical step in successful resolution of inflammation. The chemokine CXCL8 plays a central role in recruiting neutrophils. A characteristic feature of CXCL8 is its ability to reversibly exist as both monomers and dimers, but whether both forms exist in vivo, and if so, the relevance of each form for in vivo function is not known. In this study, using a 'trapped' non-associating monomer and a non-dissociating dimer, we show that (i) wild type (WT) CXCL8 exists as both monomers and dimers, (ii) the in vivo recruitment profiles of the monomer, dimer, and WT are distinctly different, and (iii) the dimer is essential for initial robust recruitment and the WT is most active for sustained recruitment. Using a microfluidic device, we also observe that recruitment is not only dependent on the total amount of CXCL8 but also on the steepness of the gradient, and the gradients created by different CXCL8 variants elicit different neutrophil migratory responses. CXCL8 mediates its function by binding to CXCR2 receptor on neutrophils and glycosaminoglycans (GAGs) on endothelial cells. On the basis of our data, we propose that dynamic equilibrium between CXCL8 monomers and dimers and their differential binding to CXCR2 and GAGs mediates and regulates in vivo neutrophil recruitment. Our finding that both CXCL8 monomer and dimer are functional in vivo is novel, and indicates that the CXCL8 monomer-dimer equilibrium and neutrophil recruitment are intimately linked in health and disease.

Original languageEnglish (US)
Article numbere11754
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - 2010

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Neutrophil Infiltration
Dimers
neutrophils
Neutrophils
Monomers
Lab-On-A-Chip Devices
Glycosaminoglycans
Interleukin-8B Receptors
glycosaminoglycans
Virus Diseases
Interleukin-8
Bacterial Infections
Endothelial Cells
interleukin-8
Inflammation
endothelial cells
Endothelial cells
Health
Wounds and Injuries
inflammation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Monomeric and dimeric CXCL8 are both essential for in vivo neutrophil recruitment. / Das, Sandhya Thulasi; Rajagopalan, Lavanya; Guerrero-Plata, Antonieta; Sai, Jiqing; Richmond, Ann; Garofalo, Roberto; Rajarathnam, Krishna.

In: PLoS One, Vol. 5, No. 7, e11754, 2010.

Research output: Contribution to journalArticle

Das, Sandhya Thulasi ; Rajagopalan, Lavanya ; Guerrero-Plata, Antonieta ; Sai, Jiqing ; Richmond, Ann ; Garofalo, Roberto ; Rajarathnam, Krishna. / Monomeric and dimeric CXCL8 are both essential for in vivo neutrophil recruitment. In: PLoS One. 2010 ; Vol. 5, No. 7.
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