Mechanism of action of AC-1370 on phagocyte functions

Abstract

The mechanism of action of a new semisynthetic cephalosporin AC-1370 on phagocyte functions was investigated. AC-1370 enhanced phagocytic functions of macrophages and neutrophils. AC-1370 bound to 27.4% of mouse peritoneal resident cells. Most of the AC-1370-binding cells were macrophages, and few neutrophils bound AC-1370. Culture supernatant of mouse macrophages cultured with AC-1370 significantly augmented phagocytic functions of mouse neutrophils. This activity of the culture supernatant of AC-1370-stimulated macrophages was abolished by digestion with trypsin but not by heat treatment at 56 degrees C for 30 min. The mechanism of the activation of phagocyte functions by AC-1370 is proposed as follows. First, AC-1370 binds to macrophages and causes their activation. Second, trypsin-sensitive and heat-stable soluble factor(s) is released from these macrophages. And finally, neutrophil functions are activated by the factor(s).