Macrophages

1. Macrophages The scavengers inside

2. Introduction Macrophages are tissue-resident professional phagocytes and antigen-presenting cells ( APC). They differentiate from circulating peripheral blood monocytes. They perform important active and regulatory functions in innate as well as adaptive immunity

3. Monocytes Monocytes are formed in Bone marrow and then stored in spleen. They are the largest corpuscles in blood. They stay in the form of monocyte till the are circulating in the blood. In case of damaged tissue, nearby mast cells secrete histamine which causes Vasodilation epithelial walls are become porous. Monocytes roll along the walls and eventually squeeze through the gaps. This process is called Diapedesis . Monocytes are attracted to the source of chemokines ( chemotaxis ).

4. From Monocyte to macrophage The chemicals secreted by damaged cells , mast cells; high conc. of LDL; bacterial by products etc. promote upregulation of adhesion molecules on the endothelial cells (EC). Thus monocyte and lymphocyte recruitment is initiated . Upregulated exposure of adhesion molecules ,and chemoattractant production and release are essential elements of the transfer of monocytes to the intima and the concurrent differentiation of these cells into macrophages . Thus the differentiation of monocytes into macrophages is a chemical process.

5. Functions : phagocytosis (paracrine) Removal of necrotic cell debris from lungs, spleen, bone, liver, neural tissue is one very important task of macrophages. This is done by fixed macrophages. For example connective tissue – histiocytes & giant cells ● liver sinusoids – Kupffer's cells ● lung – alveolar macrophages / Dust cells ● lymph nodes – free and fixed macrophages ● spleen – sinusoidal lining cells ● bone marrow – osteoclast/osteoblast ● serous fluids –pleural and peritoneal macrophages ● skin – histiocytes , Langerhans's cell

6. Functions : Adaptive Immunity When a macrophage ingests a pathogen, the pathogen becomes trapped in a phagosome , which then fuses with a  lysosome. Macrophages can digest more than 100 bacteria before they finally die due to their own digestive compounds . After digesting the pathogen , macrophage will present the   antigen   of the pathogen to the corresponding  helper T cell. The presentation is done by integrating it into the cell membrane and displaying it attached to an MHC class II molecule, indicating to other white blood cells that the macrophage is not a pathogen, despite having antigens on its surface .

7. Functions : Secretions As secretory cells, monocytes and macrophages are vital to the regulation of immune responses and the development of inflammation . They produce a wide array of powerful chemical substances ( monokines ) like: -Enzymes , complement proteins -Regulatory factors such as interleukin-1. At the same time, they carry receptors for  lymphokines  that allow them to be activated into single-minded pursuit of microbes and tumour cells .

8. Function : muscle regulation - This happens in multiple steps. -The first wave of phagocytic macrophages degrades and engulfs the injured muscle fibres and the debris. (during times of increased muscle usage ) (ED1+) -The second wave of non-phagocytic macrophages spreads among the muscle fibres and releases chemicals which stimulate proliferation of muscles .(ED2+) ( It is thought that macrophages release soluble substances that influence the proliferation, differentiation, growth, repair, and regeneration of muscle, but at this time the factor that is produced to mediate these effects is unknown .  It is known that macrophages' involvement in promoting tissue repair is not muscle specific; they accumulate in numerous tissues during the healing process phase following injury .) suspected factors : Thrombospondin-1, TGF-alpha

9. the  determinism  theory states that colony stimulating factors and other factors of the haematopoietic microenvironment determine the cells to follow a certain path of cell differentiation . In stochastic theory Undifferentiated blood cells are determined to specific cell types by randomness. The haematopoietic microenvironment prevails upon some of the cells to survive and some, on the other hand, to perform apoptosis and die. By regulating this balance between different cell types, the bone marrow can alter the quantity of different cells to ultimately be produced. Differentiation

10. Types of macrophages (on the basis of activation mechanism) M1 (classically activated macrophages) -Pro-inflammatory phenotype (accelerate inflammation) -activated by type2 interferon (IFN-gamma) and tumor necrosis factor(alpha) -released by all due to presence of pathogens M2(alternatively activated macrophages) -anti-inflammatory phenotype -activated by Interlukin 4, interferon type 1(IFN-alpha) -released by CD4+ T cells (helper T cell)

11. Types of macrophages Differentiation of monocyte ( irf = interferon regulatory facots , ppar = Peroxisome proliferator-activated receptor)

12. Other details The movement of Macrophages is amoeboid movement ( The cytoplasm slides and forms a pseudopodium in front to move the cell forward .) This how they are able to engulf pathogens, necrotic debris and tumor byproducts. Macrophages also engulf the unnecessary fat molecules in adipose tissue and a disorder in that aspect can cause atherosclerosis. Proliferation of macrophages is used to control this problem.

13. References -Wikipedia articles for monocytes, macrophages, haematopoiesis etc -”Human Monocytes and Neutrophils Store Transforming Growth Factor-α in a Subpopulation of Cytoplasmic Granules” by Calafat , Janssen, Knol , Egesten -http://www.copewithcytokines.de/cope.cgi?key=macrophages 2234 5PM.