Complement and tumor necrosis factor-α contribute to Mac-1 (CD11b/CD18) up-regulation and systemic neutrophil activation during endotoxemia in vivo

Document Type

Journal Article

Publication Date

1-1-1994

Journal

Journal of Leukocyte Biology

Volume

55

Issue

1

DOI

10.1002/jlb.55.1.105

Keywords

inflammation; liver injury; sepsis

Abstract

The increased expression of Mac-1 (CD11b/CD18) adhesion glycoproteins on neutrophils was studied using flow cytometry in male Fischer 344 rats treated with 5 mg/kg Salmonella enteritidis endotoxin. A rapid and sustained threefold increase of Mac-1 expression was observed after endotoxin injection. Inhibition of complement activation with the soluble complement receptor type 1 (sCR1) completely suppressed the initial up-regulation of Mac-1 (≤ 15 min) but did not prevent the activation during the later phase (30-90 min). During that time period, Mac-1 expression increased in parallel with the concentration of tumor necrosis factor α (TNF-α) in plasma and could be significantly attenuated with TNF antiserum. To verify the results, isolated human neutrophils were incubated with rat plasma obtained at various times after endotoxin injection. sing shape change as indicator of neutrophil activation, complement and TNF-α could be identified as responsible mediators for neutrophil activation during endotoxemia in vivo. In contrast, the massive neutrophil accumulation in the liver after endotoxin was only slightly reduced by sCR1 and unaffected by TNF antiserum. It is concluded that Mac-1 up-regulation on neutrophils after endotoxin injection in vivo may have limited relevance for hepatic neutrophil infiltration but may be important for the pathogenesis of endotoxin-induced liver injury by facilitating adherence-dependent neutrophil cytotoxicity.

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