Regulation of platelet activating factor-induced equine platelet activation by intracellular kinases.

This research investigates how certain intracellular kinases regulate horse platelet activation caused by the platelet activating factor (PAF), especially how this is affected by the presence of a bacteria-derived substance (LPS – lipopolysaccharide). The results suggest that inhibiting one particular kinase (p38 MAPK) may be beneficial in treating horse endotoxemia (a serious systemic infection), although it may not significantly affect platelet activation not enhanced by this substance.

The Role and Regulation of Intracellular Kinases

Equine platelets can be activated either directly by lipopolysaccharide (LPS), a bacterial endotoxin, or indirectly via the platelet activating factor (PAF), a proinflammatory molecule. Three kinases, or enzymatic proteins that regulate other proteins, play a certain role in this process:

• p38 mitogen-activated protein kinase (MAPK)
• Phosphatidylinositol-3 kinase (PI3K)
• Protein kinase C (PKC)

This study used selective inhibitors to assess the involvement of these kinases in equine platelet reactions to PAF, as well as the modifications to these reactions caused by LPS.

Experimental Results and Interpretation

The results demonstrated considerable interaction between these kinases and equine platelet response.

• PAF-induced the release of serotonin (5-HT), increasing when LPS was also present. The presence of the p38 MAPK inhibitor, SB203580, reduced this increase.
• Apart from that interaction, SB203580 did not affect reactions to PAF alone.
• The PKC inhibitor drastically reduced PAF-induced release of 5-HT, production of thromboxane, and platelet aggregation.
• Two PI3K inhibitors also caused noteworthy inhibition of PAF-induced platelet aggregation.

Implications for Equine Endotoxaemia

Considering the above results, this study suggests that inhibition of p38 MAPK, specifically, could be advantageous in the treatment of equine endotoxaemia by counteracting some LPS effects. However, the negative effects of platelet activation mediated by PAF, but not amplified by LPS, i.e., those that occur in the absence of bacterial infection, are unlikely to be significantly impacted by inhibiting p38 MAPK.