Role of platelet activating factor (PAF) on leukocyte-independent plasma extravasation and mast cell activation during endotoxemia

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Introduction

Independently from leukocyte adherence, endothelial factors and mast cell activation promote microvascular permeability [1]. The platelet activating factor (PAF) has been shown to play a significant role in endotoxin-induced leukocyte adherence [2]. The aim of our study was to investigate if there is also a role of PAF in mediating leukocyte-independent microvascular permeability changes and activation of mast cells during endotoxemia. Therefore, during endotoxemia, microvascular permeability and mast cell activation were determined after inhibition of the L-selectin mediated leukocyte-adherence by fucoidin and after inhibition of PAF effects by the the PAF receptor antagonist BN52021.

Methods

In male Wistar rats, microvascular permeability (MP), leukocyte adherence (LA) and mast cell activation (MCA) were determined in mesenteric postcapillary venules using intravital microscopy at baseline and at 60 and 120 min after the start of a continuous infusion of endotoxin (ETX; 2 mg/kg/hr, E. coli O26:B6) (group A, n=10). Leukocyte-endothelial interaction was blocked using fucoidin (25 mg/kg b.w.). In addition to the procedure in group A, group B (n=10) received BN52021 (5 mg/kg b.w.) after baseline measurements. Group C (n=10; control group) only received equivalent volumes of NaCl 0.9%. Statistical analysis was performed using student's t-test. A P-value <0.05 was considered significant.

Results

In groups A and B, fucoidin prevented LA, and so there were no significant differences in LA between these groups. In group A, MP and MCA significantly increased starting at 60 min (P<0.05 vs baseline). There was no significant increase in MP and MCA in groups B and C. Differences between groups A and B in MP and MCA were significant at 120 min.

Conclusions

The results of this study demonstrate that PAF plays a significant role in the initiation of endotoxin-induced leukocyte-independent plasma extravasation and mast cell activation.