Oxygen radicals are not a prerequisite for neutrophil-mediated increased vascular permeability

Abstract

The neutrophil granulocyte is considered to play a key role in the inflammatory process, contributing to the increased microvascular permeability and tissue damage seen at inflammatory sites. The mechanism underlying this process is unknown, but studies in vitro using cultured endothelium and blood polymorphonuclear granulocytes (PMNs) point to an involvement of oxygen-free radicals. In this study, we have used the hamster cheek pouch microcirculatory model to evaluate the impact of radical scavenging enzymes, superoxide dismutase (SOD), and catalase on the microvascular inflammatory reactions induced by leukotriene B4 (LTB4), which is known to induce PMN-dependent plasma leakage in this model. The variables studied were leukocyte adhesion in postcapillary venules, macromolecular permeability as leakage of fluorescent dextran, and emigration of PMNs. SOD and catalase were given in high doses as intravenous infusion and also as superfusion over the cheek pouch. All studied variables increased dramatically upon superfusion of LTB4 (4 nM) over the cheek pouch preparation and remained elevated throughout the 30-minute exposure period. Treatment with SOD and/or catalase did not influence this inflammatory response to LTB4. Nor did SOD and catalase influence the plasma leakage and emigration of PMNs caused by superfusion of the synthetic chemotactic peptide, formylmethionylleucylphenylalanine (400 nM) which from other animal models is known to induce a PMN-dependent plasma leakage. Although free radicals might contribute to the tissue damage seen at some inflammatory sites, we conclude that they are not crucially involved in the interaction between the PMN and the microvascular endothelium induced by the inflammatory mediators LTB4 and formylmethionylleucylphenylalanine, and are thus not a prerequisite for PMN-dependent microvascular permeability.