Analysis of receptor-ligand pairings and distribution of myeloid subpopulations across the animal kingdom reveals neutrophil evolution was facilitated by colony-stimulating factors

AbstractNeutrophils or heterophils constitute the largest population of phagocytic granulocytes in the blood of mammals and birds. The development and function of neutrophils and monocytes is primarily governed by the granulocyte colony-stimulating factor receptor family (CSF3R/CSF3) and macrophage colony-stimulating factor receptor family (CSF1R/IL34/CSF1) respectively. Using various techniques this study considered how the emergence of receptor:ligand pairings shaped the distribution of blood myeloid cell populations. Comparative gene analysis supported the ancestral pairings of CSF1R/IL34 and CSF3R/CSF3, and the emergence of CSF1 later in tetrapod lineages after the advent of Jawed/Jawless fish. Further analysis suggested that the emergence of CSF3 lead to reorganisation of granulocyte distribution between amphibian and early reptiles. However, the advent of endothermy likely contributed to the dominance of the neutrophil/heterophil in modern-day mammals and birds. In summary, we show that the emergence of CSF3R/CSF3 was a key factor in the subsequent evolution of the modern-day mammalian neutrophil.Impact statementColony-stimulating factors (CSFs) are important for myeloid phagocyte development. The emergence of CSF3/CSF3R in tetrapod lineages has uniquely contributed to physical, functional and structural adaptions observed in mammalian neutrophils.

Download Full-text

In-silico analysis of myeloid cells across the animal kingdom reveals neutrophil evolution by colony-stimulating factors

eLife ◽

10.7554/elife.60214 ◽

2020 ◽

Vol 9 ◽

Author(s):

Damilola Pinheiro ◽

Marie-Anne Mawhin ◽

Maria Prendecki ◽

Kevin J Woollard

Keyword(s):

In Silico Analysis ◽

Myeloid Cell ◽

Colony Stimulating Factor ◽

Key Factor ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

And Function ◽

Stimulating Factor ◽

Silico Analysis ◽

Receptor Family

Neutrophils constitute the largest population of phagocytic granulocytes in the blood of mammals. The development and function of neutrophils and monocytes is primarily governed by the granulocyte colony-stimulating factor receptor family (CSF3R/CSF3) and macrophage colony-stimulating factor receptor family (CSF1R/IL34/CSF1) respectively. Using various techniques this study considered how the emergence of receptor:ligand pairings shaped the distribution of blood myeloid cell populations. Comparative gene analysis supported the ancestral pairings of CSF1R/IL34 and CSF3R/CSF3, and the emergence of CSF1 later in lineages after the advent of Jawed/Jawless fish. Further analysis suggested that the emergence of CSF3 lead to reorganisation of granulocyte distribution between amphibian and early reptiles. However, the advent of endothermy likely contributed to the dominance of the neutrophil/heterophil in modern-day mammals and birds. In summary, we show that the emergence of CSF3R/CSF3 was a key factor in the subsequent evolution of the modern-day mammalian neutrophil.

Download Full-text

The Potential Role of Recombinant Hematopoietic Colony-Stimulating Factors in Preventing Infections in the Immunocompromised Host

Canadian Journal of Infectious Diseases ◽

10.1155/1991/782768 ◽

1991 ◽

Vol 2 (2) ◽

pp. 74-88 ◽

Cited By ~ 1

Author(s):

James Rusthoven

Keyword(s):

Bone Marrow ◽

Interleukin 1 ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Cell Recovery ◽

Colony Stimulating Factors ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

And Function ◽

Stimulating Factor

Hematopoietic colony-stimulating factors coordinate the proliferation and maturation of bone marrow and peripheral blood cells during normal hematopoiesis. Most of these factors are now available as recombinant human colony-stimulating factors, and preclinical and clinical testing is proceeding rapidly. Granulocyte and granulocyte/macrophage colony-stimulating factors have been the most extensively studied to date. In human clinical trials, granulocyte colony-stimulating factor improves neutrophil counts and function, reduces episodes of febrile neutropenia, improves neutrophil recovery after disease- or treatment-induced myelosuppression, and reduces the number of serious infections in several neutropenic disease states. Granulocyte/macrophage colony-stimulating factor has similar biological properties but may also improve eosinophil proliferation and function, and platelet cell recovery after myelotoxic bone marrow injury, Interleukin-1 boosts the effects of granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor, but also may promote the resolution of established infections in conjunction with antibiotics. The therapeutic realities and future therapeutic implications of these agents for the therapy of infections, cancer and hemopoietic disorders are discussed.

Download Full-text

Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.4.l650 ◽

1996 ◽

Vol 270 (4) ◽

pp. L650-L658 ◽

Cited By ~ 39

Author(s):

M. Ikegami ◽

T. Ueda ◽

W. Hull ◽

J. A. Whitsett ◽

R. C. Mulligan ◽

...

Keyword(s):

Protein A ◽

Surfactant Protein ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

And Function ◽

Stimulating Factor ◽

Deficient Mice ◽

Surfactant Metabolism

Mice made granulocyte macrophage-colony stimulating factor (GM-CSF)-deficient by homologous recombination maintain normal steady-state hematopoiesis but have an alveolar accumulation of surfactant lipids and protein that is similar to pulmonary alveolar proteinosis in humans. We asked how GM-CSF deficiency alters surfactant metabolism and function in mice. Alveolar and lung tissue saturated phosphatidylcholine (Sat PC) were increased six- to eightfold in 7- to 9-wk-old GM-CSF-deficient mice relative to controls. Incorporation of radiolabeled palmitate and choline into Sat PC was higher in GM-CSF deficient mice than control mice, and no loss of labeled Sat PC occurred from the lungs of GM-CSF-deficient mice. Secretion of radiolabeled Sat PC to the alveolus was similar in GM-CSF-deficient and control mice. Labeled Sat PC and surfactant protein A (SP-A) given by tracheal instillation were cleared rapidly in control mice, but there was no measurable loss from the lungs of GM-CSF-deficient mice. The function of the surfactant from GM-CSF-deficient mice was normal when tested in preterm surfactant-deficient rabbits. GM-CSF deficiency results in a catabolic defect for Sat PC and SP-A.

Download Full-text

Cytoplasmic Domains of the Human Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF) Receptor β Chain (hβc) Responsible for Human GM-CSF-induced Myeloid Cell Differentiation

Journal of Biological Chemistry ◽

10.1074/jbc.273.31.19411 ◽

1998 ◽

Vol 273 (31) ◽

pp. 19411-19418 ◽

Cited By ~ 16

Author(s):

Tetsuya Matsuguchi ◽

Michael B. Lilly ◽

Andrew S. Kraft

Keyword(s):

Cell Differentiation ◽

Myeloid Cell ◽

Colony Stimulating Factor ◽

Cytoplasmic Domains ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Β Chain ◽

Stimulating Factor

Download Full-text

The Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF ) Receptor Exists as a Preformed Receptor Complex That Can Be Activated by GM-CSF, Interleukin-3, or Interleukin-5

Blood ◽

10.1182/blood.v90.8.3005 ◽

1997 ◽

Vol 90 (8) ◽

pp. 3005-3017 ◽

Cited By ~ 52

Author(s):

Joanna M. Woodcock ◽

Barbara J. McClure ◽

Frank C. Stomski ◽

Michael J. Elliott ◽

Christopher J. Bagley ◽

...

Keyword(s):

Myeloid Cell ◽

Cytokine Receptor ◽

Activation Mechanism ◽

Receptor Complex ◽

Colony Stimulating Factor ◽

Interleukin 3 ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Abstract The granulocyte-macrophage colony-stimulating factor (GM-CSF ) receptor is expressed on normal and malignant hematopoietic cells as well as on cells from other organs in which it transduces a variety of functions. Despite the widespread expression and pleiotropic nature of the GM-CSF receptor, little is known about its assembly and activation mechanism. Using a combination of biochemical and functional approaches, we have found that the human GM-CSF receptor exists as an inducible complex, analogous to the interleukin-3 (IL-3) receptor, and also as a preformed complex, unlike the IL-3 receptor or indeed other members of the cytokine receptor superfamily. We found that monoclonal antibodies to the GM-CSF receptor α chain (GMRα) and to the common β chain of the GM-CSF, IL-3, and IL-5 receptors (βc ) immunoprecipitated both GMRα and βc from the surface of primary myeloid cells, myeloid cell lines, and transfected cells in the absence of GM-CSF. Further association of the two chains could be induced by the addition of GM-CSF. The preformed complex required only the extracellular regions of GMRα and βc , as shown by the ability of soluble βc to associate with membrane-anchored GMRα or soluble GMRα. Kinetic experiments on eosinophils and monocytes with radiolabeled GM-CSF, IL-3, and IL-5 showed association characteristics unique to GM-CSF. Significantly, receptor phosphorylation experiments showed that not only GM-CSF but also IL-3 and IL-5 stimulated the phosphorylation of GMRα-associated βc . These results indicate a pattern of assembly of the heterodimeric GM-CSF receptor that is unique among receptors of the cytokine receptor superfamily. These results also suggest that the preformed GM-CSF receptor complex mediates the instantaneous binding of GM-CSF and is a target of phosphorylation by IL-3 and IL-5, raising the possibility that some of the biologic activities of IL-3 and IL-5 are mediated through the GM-CSF receptor complex.

Download Full-text