Potentiation of neutrophil aggregation by human leukocyte inhibitory factor.

The current studies were designed to extend our investigations on the ability of the lymphokine leukocyte inhibitory factor (LIF) to function as a neutrophil activator. Specifically, we investigated whether LIF could modulate neutrophil (PMN) aggregation. Aggregation was measured as the increase in light transmission using a Payton aggregometer. We found that up to 16 units of LIF was not able to directly induce PMN clumping. However, when preincubated with 0.5-16 units LIF for 10 min, PMN aggregation was significantly enhanced in a dose-dependent manner after stimulation with 10(-7) M FMLP (94.5 +/- 3.1%), 20 nM leukotriene B4 (183.1 +/- 8.2%), and 100 micrograms guinea pig serum-opsonized zymosan (29.8 +/- 8.6%). While the LIF preparation used in these studies was highly purified, specificity for the LIF effect was demonstrated by the ability of several treatments to prevent augmentation of aggregation including: (1) the competitive binding of LIF to one of its substrates: benzoyl-arginine-ethyl-ester; (2) the blocking of PMN LIF receptors with N-acetyl-D-glucosamine; and (3) phenylmethylsulfonylfluoride treatment of the LIF preparation. As aggregation is thought to represent the in vitro correlate to adherence, these studies provide further evidence for a proinflammatory role for LIF in vivo.