Macrophages are involved at all stages of the immune response. First, as already outlined, they act as rapid protective mechanism which can respond before T cell-mediated amplification has taken place. Activated macrophages play a key role in host defence against intracellular parasitic bacteria, pathogenic protozoa, fungi and helminths as well as against tumours, especially metastasing tumours. After phagocytosis, macrophages prevent intracellularly parasitic organisms from replication at least by three ways:
,
myeloperoxidase, neutral proteases and lysosomal hydrolases.
In addition, macrophages are important killer cells (K cells); by means of antibody-dependent cell-mediated cytotoxicity (ADCC) they are able to kill or damage extracellular targets. They also take part in the initiation of T cell activation by processing and presenting antigen. Finally they are central effector and regulatory cells of the inflammatory response. To fulfil these functions, macrophages in their activated state are able to produce more than one hundred of different substances (Table 1.5).
Table 1.5:
Effector and regulatory products of macrophages
Monocytes lose their myeoloperoxidase activity during
conversion to tissue macrophages, therefore microbicidal and
cytotoxic activity of macrophages is performed mainly through ROI,
and other substances which are similar to those in
neutrophils with the exemption
of thymidine, arginase and TNF-
.
However, macrophages may acquire MPO from their environment by
pinocytosis or from ingested neutrophils. In this way, especially
macrophages in inflammatory site with the intensive cell
destruction, can gain myeloperoxidase (or other peroxidase). Such
peroxidase then participates in cytotoxic mechanisms of
macrophages.
Macrophages are important producers of arachidonic acid and
its metabolites. Upon phagocytosis macrophages release up to 50%
of their arachidonic acid from membranous esterified glycerol
phospholipid. It is immediately metabolized into different types
of prostanoids. From them prostaglandins,
especially PGE
, and
prostacyclin (PGI
) are characterized
as pro-inflammatory agents:
they induce vasodilatation, act synergeticly with complement
component C5a and LTB
,
mediate fever and myalgia response to
IL-1, in the combination with bradykinin and histamine they
contribute to erythema, oedema, and
pain induction. Tromboxan TXA
is considered as an inflammatory mediator; it facilitates platelet
aggregation and triggers vasoconstriction. LTB
is the efficient
chemoatractant substance. A mixture of
LTC
, LTD
and LTE
became
known as slow-reacting substance of anaphylaxis (SRS-A). These
leukotrienes are important mediators of bronchial asthma, since
they provoke long-term contractions of bronchial smooth
muscles. More detailed data about bioactive lipids, complement,
clotting factors and cytokines will be in next chapters.
Macrophages secrete not only cytotoxic and inflammation controlling mediators but also substances participating in tissue reorganization. They include enzymes, as hyaluronidase, elastase, and collagenase, inhibitors of some of them (antiproteases), regulatory growth factors and others. Hyaluronidase, by destroying hyaluronic acid, an important component of connective tissue, reduces viscosity and thus permits greater spreading of material in tissue spaces. Hyaluronidase is therefore sometimes designated the ''spreading factor''. Elastase and collagenase are enzymes capable to split collagen and elastin, the basic members of connective proteins.