Monocytes and Macrophages

• Monocytes and macrophages constitute the mononuclear phagocyte system.

Production

• Monocytes originate in bone marrow, like granulocytes, but mature differently.
• Maturation sequence in bone marrow: PPSC -> Myeloid Stem Cell -> Monoblast -> Promonocyte -> Monocyte
• Monocytes take two to four days to mature.
• Monocytes do not have a storage pool in bone marrow
• Monocytes are released directly into peripheral blood upon maturation
• In peripheral blood, monocytes can move between the circulating and marginal pools.
• Monocytes remain in circulation for about two days before migrating into tissues, where they mature into macrophages.

Monocyte Morphology

• Monocytes are the largest leukocytes in circulation.
• Possess a highly pleomorphic nucleus, which can be round to oval, elongate (“blobby” appearance), kidney bean-shaped, or ameboid.
• Nuclear chromatin has a "lacy" appearance, smoother with less clumping than other WBCs.
• Abundant grayish-blue cytoplasm often contains vacuoles, giving a "ground glass" appearance.

Macrophage Morphology

• Macrophages, or "tissue monocytes," are not normally observed on differential blood smears because they reside in tissues.
• Nucleus may feature several prominent nucleoli.
• Nucleus shape may be oval, indented, or elongated.
• Abundant cytoplasm stains sky blue to reddish.
• Cytoplasm contains coarse, reddish granules and vacuoles of varying sizes.

Monocytes in Circulation

• Present in both marginal and circulating pools.
• Migrate through vessel walls into tissues, where they mature into macrophages.
• Monocytes do not recirculate back into the bloodstream
• Macrophages can migrate via the lymphatic system to other organs.
• Macrophages outnumber circulating monocytes in tissues by approximately 50:1.

Macrophages

• Macrophages ("tissue monocytes") are found in "filter" organs like the liver, spleen, lungs, and lymph nodes to remove foreign invaders, damaged and old blood cells, and cellular debris.
• Macrophages in tissues are long-lived, surviving for months to years.
• Macrophages are either "free" or "fixed."
• Free macrophages, also called "wandering" macrophages, move between tissues via the lymphatic system but do not return to the bloodstream.
• Fixed macrophages remain in specific tissues for the rest of their lifespan.

"Free" Macrophages

• Typically located in the pleural cavity, peritoneal cavity, synovial cavities, alveolar spaces, and inflammatory sites.

"Fixed" Macrophages

• Fixed macrophages, also called "histiocytes," migrate to and remain in specific tissues and are known by different names depending on their location:
  • Kupffer cells in the liver
  • Alveolar macrophages in the lung
  • Osteoclasts in bone
  • Microglial cells in the brain
  • Splenic macrophages in the spleen

The Mononuclear Phagocyte System (MPS)

• The MPS is comprised of monocytes ("monos") and macrophages ("macros").
• Formerly known as the Reticuloendothelial System.
• Represents the second major branch of the circulating phagocyte system.

Functions of the MPS

• Functions as a scavenger (involves phagocytosis).
• Provides antimicrobial defense (involves phagocytosis).
• Regulates the immune response (involves phagocytosis).
• Secretory.

Scavenger Role of MPS

• A major role is to clean up tissue debris from areas of necrosis, cellular remnants, antibody-coated cells, and dead cells.
• Macrophages remove old and abnormal RBCs from circulation in the spleen, also responsible for erythrophagocytosis
• Macrophages in the spleen and bone marrow clean up RBC nuclei and Howell-Jolly bodies.

Antimicrobial Role of MPS

• Monocytes and macrophages engulf and destroy common pathogens, but they respond slower than neutrophils.
• Macrophages are better phagocytes than monocytes.
• Cells of the MPS handle pathogens and debris beyond the phagocytic capability of neutrophils, including fungi, protozoa, and viruses.

Regulation of Immune Response by MPS

• Monocytes and macrophages "process" antigens (Ag), making them more antigenic.
• After phagocytizing antigens, MPS cells "present" antigen to lymphocytes.
• Lymphocytes can then destroy the antigen.

Secretory Function of MPS

• Both monocytes and macrophages secrete monokines.
• Monokines have diverse biologic activities, including:
  • Chemotaxis for neutrophils, eosinophils, and lymphocytes.
  • Cytotoxic and anti-tumor activity via action on lymphocytes.
  • Coagulation and fibrinolysis.
  • Granulocyte-Macrophage Colony-Stimulating Factors (GM-CSF) enhance granulopoiesis and monocytopoiesis by signaling the bone marrow to produce granulocytes and monocytes.

Chemotaxis of MPS Cells

• MPS cells accumulate in areas of inflammation and tissue destruction in response to chemotaxic factors, such as:
  • Blood clot by-products (Fibrin Degradation Products)
  • Dead tissue
  • Ruptured neutrophils
  • Lipid-rich membranes of some bacteria
• Monocytes can transform into macrophages while in circulation under extreme circumstances.

Monocytosis

• Characterized by an increased number of monocytes in peripheral blood.
• Observed in diseases with a persistently high need for macrophages, including:
  • RBC diseases
  • Fungal infections
  • Necrosis
  • Foreign bodies
  • Pyothorax
  • Retained placenta
• Seen with corticosteroid use (exogenous or endogenous), marked in dogs, and apparent in other species except cats
• Frequently indicates a chronic inflammatory response, which is often associated with chronic diseases and cancer.
• Monocytes can mobilize quickly in response to acute inflammation, especially viral and fungal infections.
• Can be observed in either chronic inflammation (bacterial infections) or acute inflammation (viral and fungal infections).
• "Reactive" monocytes are found in the blood of patients with severe bacterial infections, including acute bacterial endocarditis.

Monocytopenia

• Characterized by decreased numbers of monocytes in peripheral blood.
• Generally not significant due to the normally low numbers of monocytes in circulation.