EFFECTS OF ALPHA(1)-PROTEINASE INHIBITOR ON CHEMOTAXIS AND CHEMOKINESIS OF POLYMORPHONUCLEAR LEUKOCYTES - ITS POSSIBLE ROLE IN REGULATING POLYMORPHONUCLEAR LEUKOCYTE RECRUITMENT IN HUMAN-SUBJECTS

A variety of biologic products derived from bacteria, inflammatory cel ls, and active degraded proteins have been identified as having chemot actic activity essential for polymorphonuclear leukocyte (PMN) recruit ment to the site of inflammation. Little is known, however, concerning factors responsible for regulating the intensity and duration of PMN recruitment. Evidence is growing that proteinase inhibitors modify the migrating ability of PMNs, although the physiologic implications of t his have eluded clarification. In an attempt to hypothesize a role of alpha1-proteinase inhibitor (alpha1-Pi) in PMN recruitment to inflamma tory sites, we examined the effects of alpha1-Pi in different physiolo gic concentrations on PMN migration with a microchemotaxis chamber tec hnique. Alpha1-proteinase inhibitor had both stimulatory and inhibitor y effects on cell migration, depending on its concentration. The inhib itor was active in inducing both directed locomotion (chemotaxis) and nondirected locomotion (chemokinesis) in concentrations of 0.02, 0.2, and 2 mg/ml, with maximum potency in both cases at 0.2 mg/ml (correspo nding to the normal alveolor surface fluid level in the lung). Alpha1- proteinase inhibitor impaired chemotactic responsiveness to known chem oattractants at 2 and 10 mg/ml (corresponding to normal and inflammato ry blood levels, respectively) in order of potency. These results sugg est that alpha1-Pi may play a role in regulating inflammatory processe s, especially in the lung, through its stimulatory and inhibitory effe cts, depending on its concentration.