Introduction:
Macrophages are specialist cells that have developed an innate capacity to recognize subtle differences in the structure of cell surface expressed identification stages, so called molecular patters. They arrive later to a site of infection as compared to neutrophils. Unlike neutrophils (PMNs), macrophages are also longer lived and they are present in tissues as well as in blood. Macrophages patrol the body’s tissues, searching for signs of infection. When they detect a foreign protein, they set off the inflammatory response. In particular, they engulf and destroy the invader bearing that protein and secrete a suite of cytokines, some of which raise an alarm that recruits other cells to the site of infection and puts the immune system on alert.
What Do Macrophages Do?
Anti-Bacteria Activity: Macrophages are in a resting state but can be activated by bacterial products like LPS as well as cytokines secreted by activated . like IFN-y which is secreted by TH1 cells. Activated macrophages have increased phagocytic and microbicidal activity (such as oxygen dependent mechanisms that catalyzes the reduction of oxygen to superoxide anion (O2-) which generates other oxidizing agents harmful to bacterial like hydrogen peroxide). A group of antimicrobial and cytotoxic peptides known as defensins are also present in activated macrophages.
Macrophages play important role in host defense and inflammation. First, macrophages can act as effector cells in killing phagocytosed and extracellular microbes and tumor cells by producing reactive oxygen intermediates, nitric oxide (NO), and lysosomal enzymes.
Mqs endocytose particles or soluble glycoconjugates that are bound by the mannose receptor, a C-type lectin with broad carbohydrate specificty, Mqs also have a receptor for LPS.
Cytokines secreted by Macrophages:
Production of cytokines by macrophages is considered one of the important immunoregulatory functions of macrophages. Macrophages regulate the immune response of T cells through producing important cytokines such as IL-12 and IL-10. These two cytokines can enhance Th1 or Th2 cell differentiation, respectively, result in enhancing or suppressing of cell-mediated immunity. Macrophages are also progenitors of inflammatory cytokines, such as TNF-alpha, IL-1 and Il-6.
Tissue macrophages respond to the perception of microorganisms with phagocytosis of the pathogens and the production of cytokines. Among these TNFa, IL-12 p70 and IL18 induce the secretion of IFNy from NK cells. IFNy then converts macrophages harboring pathogens to a a microbicidal state, in which bactericidal agents such as NO and reactive oxygen intermediates are porduced to kill the bacteria.
Phagocytosed antigen is digested within the endocytic processing pathway into peptides that associate with class II MHC molecules which then move to the macrophage membrane. Activation of macrophages induces increased expression of both class II MHC molecules and the co-stimulatory B7 family of membrane molecules which allows macrophages to function more effectively as antigen presenting cells. Macrophages also secrete a number of proteins central to development of immune responses such as interleukin 1 which acts on and provides a costimulatory signal required for activation following antigen recognition. Thus, macrophages and facilitate each other’s activation during the immune response.
The macrophage membrane has receptors for certain classes of antibody and thus will bind better to antigen which is complexed with antibody. Thus antibody functions as an opsonin, a molecule that binds to both antigen and macrophage and enhances phagocytosis. Opsonization is the process by which particular antigens are rendered more susceptible to phagocytosis.
Macophages express substantial levels of the F4/880 antigen, and for the most part express little or no NHC class II.
Types of Macrophages:
Kupffer cells (KCs): reside within the lumen of the liver sinusoids and form the largest population of macropahges in the body. Although KCs have markers in common with other tissue resident macrophages, they perform specialized functions geared towards efficient clearance of gut dervied bacterial, microbial deris, bacterial endotoxins, immune complexes and dead cells present in portal vein blood draining from the microvascular system of the digestive tract. Efficient binding of pathogens to the KC surface is a crucial step in the first line immune defense against pathogens. A central role for KCs in the rapid clearance of pathogens from the circulation is illustrated by the significanlty increased mortality in mice depleted of KCs.
M1 versus M2 Macrophages:
The M1 macrophages are mainly polarized by T helper type 1 (Th1) cytokines and pro-inflammatory cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-1β, and IL-12. In comparison, M2 macrophages are polarized by IL-13, IL-4, macrophage colony-stimulating factor (M-CSF), and glucocorticoids and serotonin. Functionally, M1 macrophages exhibit microbicidal activity and M2 macrophages facilitate clearance of parasites, enhance tissue repair, and promote wound healing. Once polarized, M1 or M2 macrophages secrete a series of cytokines to stimulate or suppress inflammatory responses. M1 macrophages have an elevated ability to release proinflammatory cytokines, such as IL-1β, IL-6, and IL-12, and chemokines such as interferon gamma-induced protein 10 (IP-10) and CXCL9. Conversely, M2 macrophages release anti-inflammatory cytokines, like IL-10 and TGFβ, and chemokines CCL17, CCL22, and CCL24. In terms of metabolic status, M1 macrophages produce inducible nitric oxide synthase (iNOS) enzyme to catalyze L-arginine to reactive nitrogen intermediates (RNI), which promote the killing of pathogens. On the contrary, M2 macrophages stimulate arginase I (Arg I) enzyme to catalyze L-arginine into ornithine and polyamines that support tissue remodeling and fibrosis. See Metcalf