In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human...

Neutrophil-activating factor (NAF), a 72-amino acid peptide produced by human monocytes, induced plasma leakage and neutrophil accumulation after intradermal injection in rabbits (10(-11) to 10(-9) mol/site). NAF was about three times more potent than fMet-Leu-Phe, but considerably less potent than endotoxin. The response to NAF was not inhibited by the endotoxin inhibitor polymyxin B or the protein synthesis inhibitor actinomycin D. Histology of NAF-induced lesions showed large numbers of neutrophils, but no monocytes, eosinophils, basophils, or lymphocytes were observed. Intravascular neutrophil accumulation, aggregate formation, and venular wall damage were also apparent. In vitro, NAF stimulated rabbit neutrophils as shown by the release of N-acetyl-beta-glucosaminidase. This study demonstrates that NAF elicits a rapid inflammatory response in vivo with massive neutrophil emigration, which is qualitatively similar to that observed with other chemotactic agonists.