RHEOLOGICAL RESPONSE OF NEUTROPHILS TO DIFFERENT TYPES OF STIMULATION

The potential for neutrophils to obstruct microvessels was evaluated b y measuring transit of individual neutrophils through 8-mu m pores in an automated cell transit analyzer (CTA) or into micropipettes (4-8 mu m ID). Stimulation in vitro by the chemotactic agent N-formyl-methion yl-leucyl-phenylalanine (fMLP), cigarette smoke, or purified antineutr ophil 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 o bservations were complicated by changes in cell shape: progressive bip olar shape formation (after treatment with fMLP) could facilitate entr y into larger pores (similar to 8 mu m), whereas blebs induced by ciga rette smoke caused bridging of these pores with cell immobilization. T hese processes led to an underestimation of the changes in deformabili ty by the CTA. Neutrophils responded slowly to the antineutrophil cyto plasm antibodies (similar to 30 min), with a greater increase in flow resistance evaluated by a micropipette (4-6 mu m ID) than by the CTA. We conclude that the effect of neutrophil stimulation on flow through capillary-sized vessels is potentially great (with resistance typicall y increased 10-fold or even complete blockage) but may depend on the v ascular and cellular geometry and may be local or disseminated, depend ing on the rate of the theological response.