Mechanisms of platelet-neutrophil interactions and effects on cell filtration in septic shock

Linda A. Kirschenbaum, Daryl Adler, Mark E. Astiz, Rajat S. Barua, Dhanonjoy Saha, Eric C. Rackow

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

We examined the mechanisms and the adhesive molecules mediating platelet-neutrophil adhesion in patients with septic shock. Neutrophils, platelets, and platelet poor plasma (NPPP) were isolated from 12 normal volunteers. Platelets and neutrophils were stimulated with platelet poor plasma (SPPP) removed from 12 patients in septic shock. Cell adhesion was assessed by filtration through 5-μm pore filters and by flow cytometry. Blocking monoclonal antibodies were used against the platelet and neutrophil surface receptors glycoprotein complex IIb/IIIa, P-selectin, ICAM-2, CD11a; CD11b, and CD18. The filtration pressure (Pi) of cells suspended in SPPP was significantly greater than that of cells suspended in NPPP (24 ± 1.0 mmHg vs. 14 ± 1.0 mmHg; P < 0.05). The difference between the Pi of cells suspended in SPPP or NPPP (ΔPi SPPP-NPPP) in the presence of monoclonal antibodies anti-CD41, anti-CD62P, abciximab, anti-CD11a, anti-CD11b, and anti-CD18 was significantly less than the ΔPi SPPP-NPPP of cell suspensions without the addition of these monoclonal antibodies (P < 0.01). The greatest reduction in Pi occurred when platelet receptor P-selectin was blocked simultaneously with the CD11b receptor on the neutrophil as compared to all other single blocking monoclonal antibodies or combinations of monoclonal antibodies. The mean fluorescence of activated platelet CD63-PE binding to neutrophils suspended in SPPP was significantly greater than that of cells suspended in NPPP (780 ± 130 lfu vs. 295 ± 35 lfu; P < 0.05). The greatest attenuation in mean fluorescence occurred by blocking the P-selectin receptor on the platelet simultaneously with CD11b receptor on the neutrophil. We conclude that platelet-neutrophil aggregation is increased in septic shock. This aggregation is mediated by the interaction of multiple platelet and neutrophil surface receptors. The platelet receptor P-selectin and the neutrophil receptor CD11b/CD18 appear to play the most important role in these interactions.

Original languageEnglish (US)
Pages (from-to)508-512
Number of pages5
JournalShock
Volume17
Issue number6
DOIs
Publication statusPublished - Jun 2002
Externally publishedYes

    Fingerprint

Keywords

  • Glycoproteins
  • Integrins
  • Neutrophils
  • P-selectin
  • Platelets
  • Septic shock

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Kirschenbaum, L. A., Adler, D., Astiz, M. E., Barua, R. S., Saha, D., & Rackow, E. C. (2002). Mechanisms of platelet-neutrophil interactions and effects on cell filtration in septic shock. Shock, 17(6), 508-512. https://doi.org/10.1097/00024382-200206000-00012