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J Surg Res. 2000 May 1;90(1):51-7.

Inhibition of alveolar neutrophil immigration in endotoxemia is macrophage inflammatory protein 2 independent.

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  • 1Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Abstract

BACKGROUND:

Altered transendothelial migration and delayed apoptosis of neutrophils (PMN) have been implicated as contributing to infection in patients with gram-negative sepsis. Macrophage inflammatory protein 2 (MIP-2) signals PMN immigration and may alter other PMN functions. We tested the hypothesis that sequential endotoxin challenge in vivo alters PMN apoptosis and chemotactic responses.

MATERIALS AND METHODS:

Endotoxemia was induced in male Wistar rats (250 g) via intraperitoneal (IP) administration of LPS (4 mg/kg). After 18 h, intratracheal (IT) injection of LPS (400 microg/kg) was performed. Control animals received saline injections. Four hours after IT-LPS, circulating and bronchoalveolar lavage (BAL) PMN were isolated. PMN yields were calculated, and apoptosis was quantified after 18 h in culture by annexin V-fluorescein isothiocyanate FACS analysis. BAL MIP-2 concentrations were determined by ELISA. PMN chemotaxis to MIP-2 and IL-8 was determined using a fluorescent in vitro migration assay.

RESULTS:

Endotoxemia (IP-LPS) significantly decreases BAL PMN yield in response to an in vivo IT-LPS challenge. IT-LPS inhibits BAL PMN apoptosis to the same extent as sequential IP/IT-LPS. Alveolar MIP-2 concentrations are similar in the two groups. In vitro migration to IL-8 and MIP-2 was inhibited in PMN from endotoxemic versus control animals.

CONCLUSIONS:

These data demonstrate that endotoxemia inhibits PMN migration despite similar MIP-2 concentrations in the alveolus. Sequential insults do not affect the inhibition of apoptosis. In vitro, PMN from endotoxemic animals display impaired chemotaxis to MIP-2 and interleukin-8. This may result in an inadequate host defense that contributes to increased ICU-acquired pneumonia in septic patients.

Copyright 2000 Academic Press.

PMID:
10781375
[PubMed - indexed for MEDLINE]
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