Defective neutrophil locomotion in human blastomycosis: evidence for a serum inhibitor

Unstimulated or stimulated locomotion, bactericidal, and metabolic activities of polymorphonuclear leukocytes (PMN) from 12 nonimmunosuppressed patients with invasive fungal infections proved by culture, were evaluated before and after treatment of the patients with antimicrobial drugs. The major observation was that PMN from patients with blastomycosis had a defect in stimulated locomotion. The specificity of the defect for blastomycosis was substantiated by the normal stimulated locomotion of PMN from uninfected control subjects or untreated patients with histoplasmosis, cryptococcosis, coccidioidomycosis, or sporotrichosis. The defect was due to a heat-stable, cell-directed, reversible serum inhibitor. In unheated or heated serum from untreated patients with blastomycosis, control PMN had decreased stimulated locomotion. Multiple washing followed by addition of control serum corrected locomotion of PMN from untreated patients with blastomycosis. The abnormality was not present in PMN from patients who had been treated with amphotericin B or had spontaneous resolution of their infections. Inhibition was not due to absence of chemoattractant activity because zymosan-activated patient serum or mixtures of patient and control serum stimulated PMN locomotion normally. The defect did not correlate with age, sex, neutrophil count, nitroblue tetrazolium reduction, serologic reactivity, or duration or severity of infection. No defect was found in bactericidal or metabolic activities of various combinations of PMN and serum from untreated or treated patients with blastomycosis or the 4 other fungal infections tested, indicating that the inhibitor was specific for stimulated locomotion.