Structure and properties of a novel neutrophil-activating factor (NAF) produced by human monocytes

Conclusions

Our studies show that stimulated human mononuclear phagocytes produce a neutrophil-activating factor (NAF). Lymphocytes do not appear to produce NAF or to influence its production. The results indicate that NAF is selective for neutrophils and induces activation via its own surface receptor through a signal transduction process to that initiated by fMLP and C5a. In functional terms, NAF may be regarded as homologous to fMLP and C5a. NAF differs, however, in several important aspects from either chemotactic peptide. It is of host origin, like C5a, but is generated by inflammatory cells (the mononuclear phagocytes) rather than by the activation of a humoral cascade. Most importantly, unlike C5a, NAF is not inactivated by peptidases in plasma or exudate and could therefore accumulate in inflamed tissues. While C5a and N-formyl-methionyl peptides are early mediators of neutrophil activation upon infection, NAF is likely to act as a second-wave mediator, generated at later stages, when a lesion is populated by mononuclear phagocytes.