Rheological response of neutrophils to different types of stimulation

The potential for neutrophils to obstruct microvessels was evaluated by measuring transit of individual neutrophils through 8-microns pores in an automated cell transit analyzer (CTA) or into micropipettes (4-8 microns ID). Stimulation in vitro by the chemotactic agent N-formyl-methionyl-leucyl-phenylalanine. (fMLP), cigarette smoke, or purified antineutrophil cytoplasm antibodies greatly increased flow resistance, but the response varied in its dependence on time and pore diameter. Cigarette smoke or fMLP caused rapid loss of cellular deformability, although observations were complicated by changes in cell shape: progressive bipolar shape formation (after treatment with fMLP) could facilitate entry into larger pores (approximately 8 microns), whereas blebs induced by cigarette smoke caused bridging of these pores with cell immobilization. These processes led to an underestimation of the changes in deformability by the CTA. Neutrophils responded slowly to the antineutrophil cytoplasm antibodies (approximately 30 min), with a greater increase in flow resistance evaluated by a micro-pipette (4-6 microns ID) than by the CTA. We conclude that the effect of neutrophil stimulation on flow through capillary-sized vessels is potentially great (with resistance typically increased 10-fold or even complete blockage) but may depend on the vascular and cellular geometry and may be local or disseminated, depending on the rate of the rheological response.