Can rise with various forms of blood cancers, infections with bacteria, protozoa, sarcoidosis, and autoimmune disease.

Monocytes eventually leave the bloodstream and become tissue macrophages, which are responsible for
removal of debris as well as defense against certain types of invaders such as fungi and TB, which cannot
be dealt with effectively by neutrophils. Unlike neutrophils, macrophages are able to regenerate their
lysosomal granules and may thus have a longer lifespan than neutrophils.

The macrophage population in a particular tissue may be maintained by three mechanisms: influx of monocytes from the circulating blood, local proliferation and biological turnover. Under normal steady-state conditions, the renewal of tissue macrophages occurs through local proliferation of progenitor cells and not via monocyte influx. Originally, it was thought that tissue macrophages were long-living cells. More recently, however, it has been shown that depending on the type of tissue, their viability ranges between 6 and 16 days. 

Inflammatory macrophages are present in various exudates. They may be characterized by various specific markers, e.g. peroxidase activity, and since they are derived exclusively from monocytes they share similar properties. The term exudate macrophages designates the developmental stage and not the functional state. 

Macrophages are generally a population of ubiquitously distributed mononuclear phagocytes responsible for numerous homeostatic, immunological, and inflammatory processes. Their wide tissue distribution makes these cells well suited to provide an immediate defence against foreign elements prior to leukocyte immigration. Because macrophages participate in both specific immunity via antigen presentation and IL-1 production and nonspecific immunity against bacterial, viral, fungal, and neoplastic pathogens, it is not surprising that macrophages display a range of functional and morphological phenotypes. 

Intracellular environment is unsuitable for microbial reproduction due to low pH and lack of nutrients in a phagolysosome. 
The toxic reaction may be activated to against dividing organisms. This include ROI, hypochlorite,  , myeloperoxidase, neutral proteases and lysosomal hydrolases. 

Macrophages may also produce microbiostatic effector molecules at a steady-state and thus maintain intracellular microorganisms in the non-replicating state. This latent infection is generally observed only in such individuals whose macrophages cannot be sufficiently activated. Generally, macrophages represent the second line of defence against different agent including pathogenic microorganisms. 

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

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.