The Role of Filgrastim
Howard J.A. Carp in Recurrent Pregnancy Loss, 2020
G-CSF belongs to the group of colony stimulating factors (CSFs), macrophage colony-stimulating factor (M-CSF or CSF1), granulocyte-macrophage stimulating factor (GM-CSF or CSF2), and granulocyte colony-stimulating factor (G-CSF or CSF3). The CFSs are a group of glycoproteins that bind to specific receptors on HSCs, promoting cell proliferation and differentiation into macrophages and granulocytes. They show different structures, gene location, and different receptors. All CSFs are involved in the reproductive process from ovulation to implantation and pregnancy [2]. G-CSF is a glycoprotein of 174–180 amino acids long and with a molecular weight of 19,600 Dalton: its gene is located on the long arm of chromosome 17, in region 17q11.2-q12.8 [15]. It binds to a specific receptor, the G-CSF R or CD114, encoded by a gene on the short arm of chromosome 1 in the region 1p35–34.3. G-CSF is a protein 836 amino acids long and of 92,156 Daltons molecular weight [16]. The GCSF-R is associated with signal transduction through the JAK-STAT3 pathways. G-CSF and its receptor have been found on trophoblasts and in the decidua of several mammals, including human placenta [17,18]. An anti-abortive role has been demonstrated for G-CSF in animal models, and its depletion is indirectly involved in miscarriages [19,20]. It has also been shown that G-CSF has a positive effect on trophoblast metabolism [21]. Furthermore, G-CSF is secreted in follicular fluid and its levels correlated with oocyte competence and the implantation potential of corresponding embryos [22].
Role of Hematopoietic Growth Factors in Human Leukemias: Implication of an Autocrine Process?
Velibor Krsmanović, James F. Whitfield in Malignant Cell Secretion, 2019
To understand the relationship between growth factor secretion and cell proliferation, we shall first briefly review the characteristics of the hematopoietic growth factors. Hematopoietic growth factors are defined as polypeptide hormones acting at one or several stages of hematopoietic differentiation. Historically, the term colony stimulating factor (CSF) was based on the major biological activity observed in in vitro colony assays using normal bone marrow cells. Four human and murine CSF have thus been described, according to the type of colonies that they generate in these assays. These are G-CSF, for granulocyte-CSF, CSF-1, or M-CSF, for macrophage-CSF, GM-CSF for macrophage-granulocyte CSF, and multi-CSF, or interleukin 3 (IL-3) (Table 1). It has recently become evident that, in addition to these CSF, several lymphokines or interleukins (Table 2) have either a direct or indirect hematopoietic activity, both in vitro and in vivo. Cloning of the corresponding genes and the production of the factors either in bacterial or mammalian cells has allowed the identification of their specific hematopoietic activities in vitro. Their roles in vivo are also becoming more clearly understood, through experimentation in animals and, more recently, through clinical trials in human patients.
Myeloid Growth Factors in the Lung
Jason Kelley in Cytokines of the Lung, 2022
Colony-stimulating factors are produced by many cell types, including activated T cells and monocytes (Metcalf, 1985; Clark and Kamen, 1987; Lee et al., 1990). In addition, it is apparent that tissue structural cells, which we take to include fibroblasts, epithelial, and endothelial cells, as well as smooth-muscle cells, can synthesize and release CSFs, particularly upon stimulation with inflammatory cytokines, such as IL-1 and TNF (Zucali et al., 1986; Bagby et al., 1986; Seelentag et al., 1987, 1989, Broudy et al., 1987; Kaushansky 1988a; Marini et al., 1991). In the course of our investigations on the pathogenesis of idiopathic pulmonary fibrosis (IPF), we have established several primary fibroblast lines derived from fibrotic lung tissue as well as normal adult lung tissue (Jordana et al., 1988). In addition, we have established fibroblast and epithelial cell lines from other chronically inflamed airways tissue—nasal polyps and allergic rhinitis mucosa (Ohtoshi et al., 1991a; Vancheri et al., 1991), and epithelial cell lines from bronchial mucosa (Cox et al., 1991). Nasal polyps share many of the histological derangements seen in interstitial pulmonary fibrosis (IPF), including chronic inflammatory cell infiltrates, thickening of the basement membrane, and fibroblast hyperplasia and fibrosis (Cauna et al., 1972; Connell, 1979; Kakoi and Hiraide, 1987). Indeed, nasal polyp biopsies can serve as a more ready source of tissue to examine processes involved in chronic inflammatory disorders of the respiratory tract.
Colony stimulating factors for prophylaxis of chemotherapy-induced neutropenia in children
Published in Expert Review of Clinical Pharmacology, 2022
Another type of human colony stimulating factor is granulocyte-macrophage colony stimulating factor (GM-CSF). One example is sargramostim (Table 1). Similarly, GM-CSF is used to promote hematopoiesis and stimulate cellular and humoral immunity. Sargramostim stimulates hematopoietic precursor cells and increases neutrophil, eosinophil, megakaryocyte, macrophage, and dendritic cell production [24]. Compared to G-CSF, GM-CSF has similar efficacy with no difference in time to ANC recovery [27]. However, sargramostim is associated with higher frequency of clinically significant adverse effects than filgrastim such as low-grade fever, bone pain, injection site reactions, rash, headache, and diarrhea. Overall, sargramostim and filgrastim may be therapeutically equivalent and interchangeable in hospitalized patients with chemotherapy-induced neutropenia [27].
Cytokine control of megakaryopoiesis
Published in Growth Factors, 2018
Kira Behrens, Warren S. Alexander
The primary roles of the colony-stimulating factors: granulocyte (G)-colony-stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, macrophage (M)-CSF and IL-3 (or multi-CSF), are the coordination of granulocyte and macrophage development and function. In megakaryopoiesis, while G-CSF and M-CSF have no marked effects, GM-CSF and in particularly IL-3 promote MkP cell proliferation in vitro (Ishibashi et al., 1990; Metcalf et al., 1986b), particularly in combination with other cytokines, such as members of the IL-6 family, stem cell factor (SCF) and Erythropietin (Epo). However, while IL-3 has modest thrombopoietic activity when administered in vivo (Metcalf et al., 1986a), GM-CSF administration does not elevate platelet counts (Ishibashi et al., 1990), and platelet counts are normal in mice lacking these cytokines or their receptors (Mach et al., 1998; Stanley et al., 1994). In addition, the actions of IL-3 and GM-CSF do not contribute to basal platelet levels in the absence of Tpo signalling (Chen et al., 1998; Scott et al., 2000).
Multiomic analysis of cytokines in immuno-oncology
Published in Expert Review of Proteomics, 2020
The group of cytokines predominantly involved with both normal and malignant hematopoiesis have been described as named growth factors based on their regulation of cell maturation [35,36]. These factors include: granulocyte colony stimulating factor (G-CSF), granulocyte–monocyte colony stimulating factor (GM-CSF) macrophage colony-stimulating factor (M-CSF) also known as CSF-1), and stem cell factor (SCF) [35]. Other cytokines such as IL-3, IL-5, IL-8, IL-1 can help to differentiate immature hematopoietic cells from their precursors [4,35–37]. Chemokines are a special family of heparin–binding cytokines with the ability to induce directed chemotaxis in leukocytes and nearby responsive cells. Monocyte chemoattractant protein-1 (MCP) 1 and IL-8 belong to this group of chemokines [37,38]. These chemokines are classified according to their structure (Table 1) and their homology in relation to the cysteine residues near the N-terminus in several subfamilies which include the C-C motif ligand (CCL), C-X-C motif ligand (CXCL), or CX3CL [38,39]. Chemokines are of enormous interest in oncology since they regulate not only the migration of tumor cells and macrophage adhesion, but also modulate the metastatic potential of cancer cells; through their interactions with the tumor and their microenvironment, by inducing additional cytokine secretion, and controlling cell proliferation, survival and senescence [39–43].
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