Chemotactic activity of recombinant human granulocyte colony-stimulating factor.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induced migration across polycarbonate filters of human polymorphonuclear leukocytes (PMN). rhG-CSF was active in inducing PMN migration at concentrations greater than or equal to 10 to 100 U/mL (7 to 70 ng/mL). rhG-CSF did not contain appreciable levels of endotoxin contamination as assessed by Limulus amebocyte assay, and Polymixin B did not affect the chemotactic activity of rhG-CSF. A monoclonal anti-G-CSF antibody blocked the induction of migration by G-CSF, thus establishing that the cytokine was responsible for the activity of the recombinant preparation. Checkerboard analysis was performed by seeding different concentrations of G-CSF above and/or below the filter and revealed that the migratory response to this cytokine was best observed in the presence of a positive concentration gradient between the lower and upper compartments of the chamber, thus indicating an actual chemotactic effect. When different migrating cells were examined, rhG-CSF was inactive on large granular lymphocytes and endothelial cells under conditions in which appropriate reference attractants were active. In contrast, rhG-CSF elicited a chemotactic response in monocytes inhibited by specific antibody. Thus, G-CSF is a chemotactic signal for phagocytes. This cytokine, when produced at inflammatory sites, may contribute to the recruitment of phagocytes from the blood compartment to amplify resistance against certain noxious agents.
Wang
J M
JM
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Chen
Z G
ZG
Colella
S
S
Bonilla
M A
MA
Welte
K
K
Bordignon
C
C
Mantovani
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003101:Collodion; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004727:Endothelium / Q000502:physiology; D005374:Filtration / Q000295:instrumentation; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D011076:Polycarboxylate Cement; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011076:Polycarboxylate Cement; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C005506:polycarbonate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003101:Collodion