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The effect of granulocyte colony‐stimulating factor (G‐CSF) on the degranulation of secondary granule proteins from human neutrophils in vivo may be indirect
Author(s) -
Xu Shengyuan,
Höglund Martin,
Venge Per
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1697.x
Subject(s) - lactoferrin , granulocyte , myeloperoxidase , degranulation , granulocyte colony stimulating factor , in vivo , medicine , endocrinology , in vitro , alkaline phosphatase , lipocalin , immunology , neutrophile , chemistry , biology , inflammation , biochemistry , enzyme , chemotherapy , receptor , microbiology and biotechnology
Granulocyte colony‐stimulating factor (G‐CSF) was administered at a dose of 7.5 or 10 μg/kg s.c. once daily for 6 d (days 1–6) to two groups consisting of eight and six healthy volunteers. The administration of G‐CSF resulted in a rapid decrease in neutrophil counts and serum levels of the secondary granule protein, human neutrophil lipocalin (HNL) after 30 min, followed by a recovery and gradual increase within 180 min. The number of circulating neutrophils and plasma and serum levels of neutrophil secondary granule proteins were dramatically elevated on day 2 (1 d after the administration of G‐CSF) and stayed so until day 7. The plasma levels of HNL and lactoferrin (LF) showed a biphasic pattern with peaks at day 2 and days 5–7, and remained highly elevated at day 12. The serum levels of HNL and LF increased rapidly (about 8‐fold and 6‐fold, respectively) on day 2 and stayed elevated until day 7, subsequently returning to baseline levels. At day 5, neutrophil release induced in vitro by f‐MLP was significantly enhanced. The cellular contents of HNL and LF were reduced to about 50% of levels before G‐CSF administration at day 5. The release of lactoferrin and HNL, but not of myeloperoxidase (MPO), was slightly enhanced after preincubation of isolated normal neutrophils with G‐CSF in vitro , but no obvious release of these proteins was observed with G‐CSF alone. The administration of G‐CSF resulted in a dramatic increase in the alkaline phosphatase (AP) activity in the plasma membrane, with maximal activity occurring at day 5. Furthermore, during administration of G‐CSF, TNF‐α in plasma increased about 25‐fold. TNF‐α started to rise at day 2 and peaked at day 6. After discontinuation of G‐CSF the levels of TNF‐α gradually decreased. The elevated levels of TNF‐α (tumour necrosis factor‐α) were temporally correlated to the other signs of neutrophil activation. GM‐CSF and IL‐8, however, were not detected in plasma. Our data suggest that G‐CSF affects the neutrophils not only directly but also indirectly by the induction of the production of other cytokines such as TNF‐α.