Effect of zymosan-activated plasma on the deformability of rabbit polymorphonuclear leukocytes.
Intravascular infusion of inflammatory mediators causes a sudden neutropenia due to the sequestration of polymorphonuclear leukocytes (PMN) within the microvasculature of the lung and other organs. This sequestration could be due to a decrease in the ability of PMN to deform and pass through the narrow capillary bed. The purpose of this study was to determine if the complement fragments present in zymosan-activated plasma (ZAP) caused a rapid stiffening of PMN. The PMN deformability was determined by measuring the pressure required to pass PMN through a polycarbonate filter containing 5-micron pores at a constant flow rate as well as the extraction of PMN compared with red blood cells and 125I-labeled albumin by the filter. The role of the cytoskeleton in PMN deformation was examined in studies where F-actin formation was inhibited using cytochalasin B or microtubule assembly was inhibited using colchicine. The results showed that treatment with ZAP induced a rapid decrease in PMN deformability. Inhibiting the formation of F-actin made the unstimulated PMN more deformable and reduced the stiffening induced by ZAP. In contrast, inhibition of microtubule reassembly did not alter either normal deformability or the ZAP-induced decrease in deformability. In vivo, colchicine increased normal PMN margination but did not inhibit the rapid sequestration of PMN induced by infusion of ZAP. These studies indicate that ZAP induces a rapid decrease in PMN deformability that is mediated through the cytoskeleton. They suggest that this decrease is due to the polymerization of F-actin.
Inano
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University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
English
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Doerschuk
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D000199:Actins / Q000096:biosynthesis; D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D003165:Complement System Proteins / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D005374:Filtration; D066298:In Vitro Techniques; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009503:Neutropenia / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000648:ultrastructure*; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D015054:Zymosan / Q000494:pharmacology*
D000199:Actins; D010446:Peptide Fragments; D003571:Cytochalasin B; D003165:Complement System Proteins; D015054:Zymosan; D003078:Colchicine