In vitro impairment of human granulocyte functions by lead

Chemotaxis and receptor independent phagocytosis of human polymorphonuclear leukocytes (PMNs) exposed to lead in vitro (concentrations between 1.2 microM and 115 microM) were studied. Chemotaxis was measured in Boyden chambers and phagocytosis was investigated using latex beads. Additional methods were also applied. Superoxide anion formation from PMNs activated with preopsonized zymosan was quantified as superoxide dismutase-inhibitable reduction of ferricytochrome c. Steady state fluorescence polarization was performed using trimethylammonium diphenylexatriene (TMA-DPH). Lead concentrations were highly correlated both with decreased chemotactic activity (r = 0.70 p less than 0.01) and with decreased phagocytosis (r = 0.68 p less than 0.01). Ferricytochrome c reduction was not significantly affected. An increase in fluorescence polarization was recorded at the highest concentration of lead used, i.e. 57.6 microM and 115 microM, both in unstimulated PMNs and in PMNs activated with N-formyl-methionyl-leucyl-phenylalanine chemotactic peptide (n-FMLP). Moreover, an increase in the fluorescence polarization was observed in PMNs pretreated with a microtubule disrupting drug, exposed to lead concentrations of 14.4 microM and 57.6 microM and then activated with n-FMLP; no increase was recorded at the lowest lead concentrations used, i.e. 1.2 microM and 3.6 microM. The possible interaction of lead with the membrane-cytoskeleton apparatus is discussed.