CXCL8 attenuates chemoattractant-induced equine neutrophil migration

Area of Science:

• Immunology
• Veterinary Medicine
• Cell Biology

Background:

• Chemokine CXCL8 is a chemoattractant with known modulatory effects on human neutrophil migration.
• Equine neutrophils play a key role in inflammatory conditions, and their migration is crucial for pathogen clearance.
• Platelet-activating factor (PAF) and leukotriene B4 (LTB4) are important chemoattractants in non-infectious equine inflammation.

Purpose of the Study:

• To investigate the effect of CXCL8 on equine neutrophil migration and adherence in response to PAF and LTB4.
• To determine if these effects are mediated by specific receptors and the role of cyclic adenosine monophosphate (cAMP).

Main Methods:

• ChemoTx plate migration assay to measure neutrophil migration.
• Adhesion assays to assess neutrophil adherence to protein-coated plastic.
• Use of CXCR1/2 antagonist SB225002 to investigate receptor mediation.
• Measurement of intracellular cAMP levels and effect of dibutyryl cAMP on migration.

Main Results:

• CXCL8, LTB4, and PAF each induced equine neutrophil migration and adhesion.
• CXCL8 attenuated neutrophil responses to PAF and, to a lesser extent, LTB4.
• The attenuation of PAF-induced responses was reversed by the CXCR2 antagonist SB225002.
• CXCL8, PAF, and LTB4 increased intracellular cAMP; CXCL8 and PAF showed additive effects.
• Dibutyryl cAMP reduced neutrophil migration induced by CXCL8 or PAF.

Conclusions:

• CXCL8 acts as a chemoattractant and pro-adhesive molecule for equine neutrophils.
• CXCL8 attenuates equine neutrophil responses to PAF and LTB4 in a CXCR2-mediated and cAMP-dependent manner.
• This modulation could lead to neutrophil trapping at inflammation sites, potentially influencing bacterial clearance or tissue damage.