Complement C5a‐Induced Changes in Neutrophil Morphology During Inflammation

• DOI: 10.1111/sji.12580
• Publication Date: 2017-06-30T15:05:24Z
• Authors: S. Denk; R. P. Taylor; R. Wiegner; E. M. Cook; M. A. Lindorfer; K. Pfeiffer; S. Paschke; T. Eiseler; M. Weiss; E. Barth; J. D. Lambris; M. Kalbitz; T. Martin; H. Barth; D. A. C. Messerer; F. Gebhard; M. S. Huber‐Lang
• Keywords: Complement; Morphology; C5a receptor

The complement and neutrophil defence systems, as major components of innate immunity, are activated during inflammation infection. For migration to the inflamed region, we hypothesized that activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure human neutrophils dose- time-dependently resulted a rapid receptor-1 (C5aR1)-dependent shape change, indicated by enhanced flow cytometric forward-scatter area values. Similar were observed after incubation with zymosan-activated serum blood murine sepsis, but not mice lacking C5aR1. In neutrophils, Amnis high-resolution digital imaging revealed C5a-induced decrease circularity increase length/width ratio. Biomechanically, microfluidic optical stretching experiments significantly increased deformability early stimulation. inhibited pharmacological blockade either Cl-/HCO3--exchanger or Cl- -channel. Furthermore, actin polymerization assays exposure polarization neutrophils. functional process triggered ATP-P2X/Y-purinoceptor interaction was also involved changes, because pretreatment suramin blocked only subsequent C5a-dependent chemotactic activity. conclusion, data suggest anaphylatoxin regulates basic cell processes increasing membrane elasticity size consequence actin-cytoskeleton reorganization, transforming into migratory able invade inflammatory site subsequently clear pathogens molecular debris.