Elucidating the role of caveolin-1 in acute inflammation

Abstract

Acute inflammation is an immediate response to bodily injury or infection. During this process, small vessels, such as postcapillary and collecting venules, serve as the principal sites of leukocyte extravasation and plasma leakage into affected tissue. Caveolin-l, the structural protein of the plasmalemmal invaginations known as caveolae, is highly expressed in endothelium and has been shown to associate with two critical mediators of acute inflammation, myeloperoxidase and the chemokine, IL-8.;In this study, we have investigated the role of caveolin-1 in the acute inflammatory response. Our results have demonstrated that there are distinct levels of caveolin-1 expression (cavhigh and cavlow) in dermal microvasculature and that cavlow vessels mediated the majority of neutrophil recruitment in response to IL-8. We have shown here that neutrophils traverse human dermal microvascular endothelial cells (HDMVECs) using either a transcellular route (directly through the cell) or a paracellular route through cellular junctions. Furthermore, we determined that the percentage of neutrophils capable of migrating along the transcellular path was dependent on the level of expression of caveolin-1 in HDMVECs. These data have revealed that within a morphologically similar collection of vessels a subpopulation, identified by low levels of caveolin-1, is targeted for neutrophil extravasation and that expression levels of caveolin-1 may influence the route of migration through the microvasculature.;In addition to leukocyte extravasation, another hallmark of acute inflammation is an increase in vascular permeability at the site of irritation or infection. We observed that caveolin-1 knockout mice had decreased vascular leakage compared to wild type animals using mustard oil and croton oil, two separate mediators of hyperemia in the mouse. Moreover, we found that the absence of caveolin-1 resulted in diminished activation of the MAP kinase family member BRK upon treatment with croton oil.;This work has described the manifold roles of caveolin-1 in the inflammatory process. Further investigation should help to elucidate the precise mechanism by which caveolin-1 facilitates transcellular migration and inhibits interstitial fluid accumulation in the acute inflammatory response.