Effects of human IgG on locomotion of human neutrophils related to IgG binding of a hydrophobic probe.

Heat-denatured (63 degrees) human IgG had complex effects on locomotion of human neutrophils. At concentrations of 1 mg/ml and below, it stimulated chemotactic locomotion into filters judged by the leading front assay, however, pre-treatment of the cells or of the filters with denatured IgG caused a reduction in the number of locomoting cells, compared to cells locomoting in a medium containing albumin. These effects took place in complement-free media. Native IgG was not chemotactic. The chemotactic activity of denatured IgG correlated well with increased binding by the same IgG preparations of the hydrophobic probe, 1-anilinonaphthalene-8-sulphonate (ANS), and it is suggested that heating induces a conformational change in the IgG molecule which allows recognition of the altered molecule by neutrophils and activation of a chemotactic response. The integrity of the Fc fragment is required for this activity. As well as a direct chemoattractant activity of IgG, evidence for release of chemotactic factors by cells in contact with aggregated IgG was also obtained. It is suggested that the contrary effects of denatured IgG on neutrophil locomotion are explicable if the protein, like other denatured proteins, activates the sensory chemotactic mechanism in the neutrophil, while at the same time causing a modification of adhesion of cell to substratum which may impair the locomotor capacity of the cells.