Vascular responses during acute neutrophilic inflammation. Their relationship to in vivo neutrophil emigration

Hyperemia, an increase in vascular permeability, and the emigration of leukocytes are the basic manifestations of the acute inflammatory reaction. Many previous studies have employed phagocytosable material to induce inflammation and neutrophil infiltration. In this study, the authors induced neutrophil infiltration into rabbit skin by injecting the soluble chemotactic stimuli, zymosan-activated plasma, C5a(desArg), N-formyl-methionyl-leucyl-phenylalanine, and factors released by Escherichia coli. During the evolution of the response, ⁵¹Cr-labeled leukocytes were used to quantitate neutrophil influx, ¹²⁵I-labeled albumin was used to quantitate permeability, and ⁸⁶Rb was used to quantitate blood flow. Simultaneous measurements showed a close correlation in time between the degree and peak rate of neutrophil influx and the degree of hyperpermeability and hyperemia. Dose-response experiments performed with 2 to 90 per cent (v/v) zymosan-activated plasma showed a direct corelation between the rate of neutrophil influx and the degree of vascular permeability and blood flow. No vascular responses were induced after injection of these chemotactic stimuli into rabbits made neutropenic with nitrogen mustard treatment. The vascular responses associated with neutrophil infiltration were inhibited by indomethacin or aspirin. It is concluded that the vascular hyperpermeability and hyperemia acompanying neutrophilic inflammatory reactions may be induced by neutrophils during their migration across the microvascular walls and that prostaglandins may in part mediate these responses. Furthermore, phagocytosis by the neutrophils is not required to induce these vascular changes.