Rheological response of neutrophils to different types of stimulation

Abstract

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.

Unique Structural Features That Influence Neutrophil Emigration Into the Lung

“…A number of investigations have provided evidence that activation of neutrophils further contributes to the failure of transit through the alveolar capillary bed (63,91,92,106,115,187,194,199,278,290), and changes in mechanical properties after activation may be of major importance. Binding of mediators such as chemotactic factors (e.g., the complement fragment C5a) to neutrophil receptors induces a transient resistance of the cells to deformation (27,35,60,62,69,115,289). Because neutrophils must deform to pass through the capillary bed, leukocyte activation by inflammatory mediators could effect further concentration of neutrophils at the alveolar walls (51,52,102,115,180,289).…”

Increased Membrane Expression of Proteinase 3 during Neutrophil Adhesion in the Presence of Anti–Proteinase 3 Antibodies

“…9 -13 They modulate neutrophil adhesion and migration 14,15 and induce F-actin polymerization and cell stiffening, ultimately leading to neutrophil retention in glomerular capillaries. [15][16][17] Although the role of ANCA in vasculitis pathogenesis has been established, the accessibility of ANCA to their antigens in blood is still debated. 18 -20 The absence of ANCA detection on neutrophils in whole blood has been proposed to result from plasma ␣1 anti-trypsin (A1AT) binding to PR3.…”

Hydrogels from Protein Engineering

“…Selectins are expressed by endothelial cells and bind to carbohydrate ligands expressed by leukocytes. Selectin-ligand binding results in leukocyte rolling behavior, in which cells weakly attach to endothelial cells along blood vessel walls [136]. Surface modification of a synthetic substrate with P-selectin supported rolling behavior of leukocyte cell mimics displaying the selectin ligand sialyl Lewis X (SLe x ) under physiological flow conditions [137].…”