Monocytes (Macrophages)
Blood Cells

Author: Gianpiero Pescarmona
Date: 25/05/2007

Description

Macrophages

(Greek: "big eaters", makros = large, phagein = eat) are cells within the tissues that originate from specific white blood cells called monocytes.

Macrophage functions

Their role is to phagocytize (engulf and then digest) cellular debris and pathogens and to stimulate lymphocytes and other immune cells to respond to the pathogen.

Macrophages activation

NADPH oxidase complex generates a respiratory burst. Superoxide can react to form hydrogen peroxide and hypochlorus acid, which together participate in bacterial killing.

Role of NADPH-Oxidase

NADPH-Oxidase activation requires Rac translocation to the membrane that is mediated by geranylgeranylation.
Nuclear Factors involved in MA.PDF
Nuclear Factors involved in MA, Abstract

Lysosomes acidification

Macrophage cytoplasmic vesicle pH gradients and vacuolar

H1-ATPase activities relative to virus infection 1998

Macrophages behavior bifurcation

Top figure: Strong lysosomes acidification, foreign antigens full digestion

Bottom figure: Poor lysosomes acidification, foreign antigens partial digestion and antigen presentation

Dendritic Cells

IL-6 and TNF alpha production by macrophages 2007

Macrophages function as a ferritin iron source for cultured human erythroid precursors 2007

Bacterial Inhibitors of V-ATPase

Macrophages Polarization

Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression1 2006

Macrophages were obtained by culturing monocytes (98% CD14+, 13% CD16+) for 7 days in RPMI 1640 (Biochrom) supplemented with 20% FCS (HyClone) and 100 ng/ml M-CSF in FCS-coated dishes at a density of 1.5 × 105/cm2. Macrophage polarization was obtained by removing the culture medium and culturing cells for an additional 18 h in RPMI 1640 supplemented with 5% FCS and 100 ng/ml LPS plus 20 ng/ml IFN-{gamma} (for M1 polarization) or 20 ng/ml IL-4 (for M2 polarization).

  • Monocytes and tissue macrophages provide both immediate defense against foreign agents and assist during the setting off and development of the adaptive immune response. Monocytes originally derive from CD34+ myeloid progenitor cells in the bone marrow, circulate in the bloodstream, and enter peripheral tissues where they mature into different types of resident macrophages, characterized by low oxygen consumption, low protein synthesis rate, and modest cytokine production.
    Inflammation due to tissue damage or infection results in resident macrophage activation, which increases the production of cytokines, chemokines, and other inflammatory mediators, as well as monocyte recruitment. In the context of specific immune response, the cytokine milieu compels mononuclear phagocytes to express specialized and polarized functional properties.
  • Mirroring the Th1/Th2 nomenclature, many refer to polarized macrophages as M1 and M2 cells.
    • Classically polarized activated M1 macrophages have long been known to be induced by IFN-γ alone or in concert with microbial stimuli as LPS, or cytokines as TNF and GM-CSF. M1 cells have an IL-12high, IL-23high, IL-10low phenotype, are proficient producers of effector molecules (reactive oxygen and nitrogen intermediates) and inflammatory cytokines (IL-1β, TNF, IL-6), contribute as inducer and effector cells in polarized Th1 responses, and mediate resistance against intracellular parasites and tumors
    • M2 form of macrophage activation is a generic name used for various forms of nonclassically activated macrophages resulting from cell exposure to IL-4 or IL-13, immune complexes, IL-10, glucocorticoid, or secosteroid (vitamin D3) hormones. The various forms of M2 macrophages share an IL-12low and IL-23low phenotype, generally display high levels of scavenger, mannose, and galactose-type receptors, and arginine metabolism is shifted to production of ornithine and polyamines via arginase.

Comments
2010-09-24T12:20:39 - Gianpiero Pescarmona

MARCO scavenger receptors bind silica

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