Two patterns of early neutrophil accumulation in acute inflammatory lesions

Abstract

A model of acute inflammation in the skin of sheep was developed using [111In]oxine-labeled neutrophils to quantify the accumulation of neutrophils in inflammatory lesions. Peak accumulation occurred during the first hour in lesions induced by zymosan-activated sheep plasma (ZAP, 100%) and during the second hour in lesions induced by endotoxin (10(-11) moles) and casein (2 x 10(-8) moles). The accumulation of neutrophils after the final stimulus diminished when lesions were restimulated every 2 h on two or more occasions. Thus desensitization of inflammatory lesions previously observed in rabbit skin is not restricted to that species. The early accumulation of neutrophils in primary and restimulated lesions was measured in lesions from 10 min to 2 h old. In primary lesions, ZAP induced significant neutrophil accumulation by 10 min, whereas 30 to 45 min elapsed before significant neutrophil accumulation occurred in lesions induced with endotoxin and casein. The initial responses in restimulated lesions were not diminished, but there was a failure of neutrophil accumulation to continue for as long as occurred in primary lesions. This finding indicates that regulation of the neutrophil influx into dermal inflammatory lesions may occur at a point after occupancy of the putative tissue receptors in the pathway which leads to accumulation of neutrophils at the injection site. The results indicate that there are at least two patterns of neutrophil accumulation in primary inflammatory lesions. The delayed pattern of neutrophil accumulation induced by casein and endotoxin resembles the enhanced binding of neutrophils to stimulated endothelial cultures in vitro, whereas the basis for the immediate response induced by ZAP remains conjectural. It is proposed that the primary action of chemotactic agents may be to provoke changes in the adhesive properties of endothelium and resident connective tissue cells thus permitting the migration of neutrophils into inflammatory lesions.