Mitogen-activated protein kinases regulate platelet-activating factor-induced hyperpermeability

Objective: The authors tested the hypothesis that p42/44- (ERK-1/2) and/ or p38-mitogen-activated protein kinases (MAPK) are in vivo regulatory elements in the platelet-activating factor (PAF) activated signaling cascade that stimulates microvascular hyperpermeability. Methods: FITC-dextran 70 was used as the macromolecular tracer for microvascular permeability in the mouse mesenteric fat tissue. Interstitial integrated optical intensity (IOI) was used as an index of permeability. Results: An application of 10^-7M PAF increased IOI from 23.1 ± 3.6 to 70.8 ± 7.4 (mean ± SEM). Inhibition of ERK-1/2 with 3 μM and 30 μM AG126 reduced IOI to 32.3 ± 2.5. Similarly, inhibition of p38-MAPK with 6 nM, 60 nM and 600 nM SB203580 lowered IOI to 29.1 ± 2.4. Conclusions: The results demonstrate that ERK-1/2 and p38MAPK participate in the signaling cascade that regulates PAF-induced microvascular hyperpermeability in vivo.