Cardiopulmonary bypass primes polymorphonuclear leukocytes

Jess D. Schwartz, Peter Shamamian, Daniel S. Schwartz, Eugene A. Grossi, Chad E. Jacobs, Federico Steiner, Peter C. Minneci, F. Gregory Baumann, Stephen B. Colvin, Aubrey C. Galloway

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28 Scopus citations

Abstract

Polymorphonuclear leukocyte (PMN) superoxide (· O2/-) production has been implicated in the pathogenesis of cardiopulmonary bypass (CPB)-related end organ injury. PMN 'priming' has been described as an event which enhances the release of · O2/- following a second, activating insult. We hypothesized that PMN priming occurs during CBP and is temporally related to the plasma level of complement (C3a), interleukin (IL)-6, and IL-8. PMNs were isolated from 10 CPB patients pre-bypass (preCPB), 5 min after protamine administration (PROT), and at 6 and 24 h post-CPB. PMN · O2- production was measured by a cytochrome c reduction assay in the presence or absence of either phorbol 12-myristate-13-acetate (PMA, 0.4 μg/ml) or N-formyl- methionyl-leucyl-phenylalanine (FMLP, 1 μM) and also after priming with 2000 nM platelet-activating factor (PAF) followed by activation with either PMA or FMLP. Plasma levels of C3a, IL-6, and IL-8 were determined by enzyme-linked immunosorbent assay. PMA-activated PMN ·O2/- production was significantly elevated at 6 h post-CPB compared to preCPB levels (11.04 ± 0.9 vs 7.62 ± 0.57, P = 0.009), indicating that CPB is associated with in vivo PMN priming. When PMNs were primed in vitro with PAF and then activated with PMA or FMLP, · O2/- release at 6 h post-CPB was also significantly greater than pre- CPB levels (16.04 ± 0.74 vs 12.2 ± 0.92, P = 0.038; and 17.33 ± 1.38 vs 13.33 ± 1.35, P < 0.05), indicating that CPB acts synergistically with PAF to prime PMNs. Levels of C3a rose significantly over pro-CPB levels at PROT (P = 0.001), and IL-6 and IL-8 rose over pre-CPB levels at 6 h post-CPB (P = 0.01 and P = 0.006, respectively). These findings demonstrate that CPB not only directly primes PMNs, but also potentiates priming of PMNs by PAF. This 'primed' PMN state, which coincided with the increased plasma levels of inflammatory mediators, may suggest a mechanism of predisposition to organ dysfunction following CPB.

Original languageEnglish (US)
Pages (from-to)177-182
Number of pages6
JournalJournal of Surgical Research
Volume75
Issue number2
DOIs
Publication statusPublished - Mar 1998
Externally publishedYes

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Keywords

  • Complement
  • Cytokines
  • Neutrophils
  • Priming
  • Superoxide

ASJC Scopus subject areas

  • Surgery

Cite this

Schwartz, J. D., Shamamian, P., Schwartz, D. S., Grossi, E. A., Jacobs, C. E., Steiner, F., ... Galloway, A. C. (1998). Cardiopulmonary bypass primes polymorphonuclear leukocytes. Journal of Surgical Research, 75(2), 177-182. https://doi.org/10.1006/jsre.1997.5287