Mechanics of stimulated neutrophils: cell stiffening induces retention in capillaries

GS Worthen, B Schwab III, EL Elson, GP Downey - Science, 1989 - science.org
GS Worthen, B Schwab III, EL Elson, GP Downey
Science, 1989science.org
The effect of peptide chemoattractants on neutrophil mechanical properties was studied to
test the hypothesis that stimulated neutrophils (diameter, 8 micrometers) are retained in
pulmonary capillaries (5.5 micrometers) as a result of a decreased ability of the cell to
deform within the capillary in response to the hydrodynamic forces of the bloodstream.
Increased neutrophil stiffness, actin assembly, and retention in both 5-micrometer pores and
the pulmonary vasculature were seen in response to N-formyl-methionyl-leucyl …
The effect of peptide chemoattractants on neutrophil mechanical properties was studied to test the hypothesis that stimulated neutrophils (diameter, 8 micrometers) are retained in pulmonary capillaries (5.5 micrometers) as a result of a decreased ability of the cell to deform within the capillary in response to the hydrodynamic forces of the bloodstream. Increased neutrophil stiffness, actin assembly, and retention in both 5-micrometer pores and the pulmonary vasculature were seen in response to N-formyl-methionyl-leucyl-phenylalanine. These changes were abolished in cells that had been incubated with 2 micromolar cytochalasin D, an agent that disrupts cellular actin organization. A monoclonal antibody directed at the CD11-CD18 adhesive glycoprotein complex did not inhibit the increase in stiffness or retention in pores. These data suggest that neutrophil stiffening may be both necessary and sufficient for the retention that is observed. Hence, neutrophil sequestration in lung and other capillaries in the acute inflammatory process may be the result of increased stiffness stimulated by chemoattractants.
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