Abstract
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 10−7 M 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.
This work was supported in part by NIH grant 5RO1 HL70634. The authors are grateful to Hiroyuki Koyama, Masatake Katsu, and Taketo Saito for helpful discussions and Atsuko Onozuka for her kind help.