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Complement and tumor necrosis factor‐ α contribute to Mac‐1 (CD11b/CD18) up‐regulation and systemic neutrophil activation during endotoxemia in vivo
Author(s) -
Witthaut Rochus,
Farhood Anwar,
Smith C. Wayne,
Jaeschke Hartmut
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.55.1.105
Subject(s) - integrin alpha m , tumor necrosis factor alpha , in vivo , biology , complement system , immunology , cd18 , lipopolysaccharide , flow cytometry , antibody , microbiology and biotechnology
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 cnteritidis 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 (sCRl) 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. Using 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 sCRl 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. J. Leukoc. Biol. 55: 105–111; 1994.