Chemotactic activity of recombinant human granulocyte colony- stimulating factor

Abstract

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.

Neutrophil function and cytokine‐specific signaling in chronic neutrophilic leukemia

“…In normal human neutrophils, fMLP increases chemotaxis activity and adhesive ability (Palmblad et al, 1981). rhG-CSF also stimulates human polymorphonuclear leukocyte (PMN) migration (Wang et al, 1988) and adhesion (Okada, Kawagishi & Kusaka, 1990). Although these chemoattractants increased chemotaxis and adhesion in our CNL case, the response rates was significantly lower than those in the control neutrophils as described previously (Kaplan et al, 1992).…”

The effects of recombinant human granulocyte‐colony stimulating factor on vascular dysfunction and splanchnic ischaemia‐reperfusion injury

“…Furthermore, the administration of rh G-CSF improved neutropenia and reduced leukocyte accumulation in the ileum and in the lung. The improvement in neutrophil count observed in SAO shocked rats treated with rh G-CSF does not seem to be the consequence of the in vitro and in vivo eects of the cytokine on proliferation and dierentation of neutrophilic lineage (Clark & Kamen, 1987;Wang et al, 1988); rh G-CSF was administered 75 min before the evaluation of peripheral neutrophil count and bone marrow myeloid precursor cells whereas it has been shown that an intravenous injection of the haematopoietic cytokine causes, after an initial neutropenia of between 5 and 30 min, neutrophilia signi®cantly evident only after 2 h and that peaks between 12 and 24 h (Ulich et al, 1988). In agreement with the kinetics of rh G-CSF haematopoietic eect, the recombinant hormone did not cause any increase in neutrophil count in sham rats or any stimulation of bone marrow myeloid precursor cells in either sham or shocked rats.…”

Effects of granulocyte‐monocyte colony‐stimulating factor (GM‐CSF) on expression of adhesion molecules and production of cytokines in blood monocytes and ovarian cancer‐associated macrophages

“…In contrast, GM-CSF augmented IL-8 production in 7 of 8 TAM preparations examined. Augmentation of chemokine production by in situ macrophages may act in concert with the attractant activity of GM-CSF itself (Wang et al, 1987) to amplify leukocyte recruitment.…”