NEW APPROACHES TO MACROPHAGE FUNCTION

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This presentation will attempt to review some of the basic characteristics and functions of macrophages andindicate newer approaches to understand these mechanisms in molecular terms. 1. Origins. Macrophages derive initially from a pluripotential stem cell in the bone marrow, transforms intoa monoblast, which, in the presence of colony stimulating factor differentiates into a promonocyte which then leavesthe bone marrow, appears in the blood as the monocyte and has the potential of localizing in the tissues. Thereare approximately 0.6-105 mouse monocytes produced per hour, and the turnover time of promonocytes is approximately 32 hours. Inflammatory reactions increase their production 1.5. While monocytes exist in the circulation for only 36 to 104 hours, they can live for very long periods of time in the tissues, as evidenced by tatoos. 2. Characteristics of monocytes. a) Functions. Macrophages are highly motile, highly endocytic cells, which ingest large particles by phagocytosis and smaller particles or liquid phase materials by pinocytosis through a variety of specific and non-specificmechanisms. b) Ten to 20% of macrophages appear to possess Ia antigens and are required for antigen presentation tosome T-cell subsets. c) Macrophages have the capability of carrying out intracellular and extracellular killing of parasites andtumor cells, digestion of intracellular materials and release of products which may be involved in tissue damage. d) Receptors and markers. Macrophages are known to possess receptors for immunoglobulins, and throughthe use of monoclonal antibodies produced by hybridomas it has been possible unambiguously to define them as beingreceptors for IgGI, IgG2a and IgG3 in the mouse. In addition they have receptors for C3b and for a variety of hormones, including insulin. e) Enzymes. The enzyme constituitively secreted by macrophages and no other blood cells is lysozyme, which becomes an important marker for identifying macrophages. In addition, they have lysosomal hydrolases whichinclude esterases, proteases, lipases, nucleases, glycocylases, amidases, hydrases, phosphoamidases, all of which workbest at the acid pH found in the lysosome, pH 3.0-4.0.3. Endocytosis. There are a number of pathways by which extracellular materials are constantly being takenup by the macrophage including fluid phase pinocytosis, adsorptive pinocytosis, and phagocytosis of larger particles. This is followed by fusion of the phagocytic or pinocytic vesicle with primary lysosomes containing proteolytic enzymes, killing and/or digestion of material in those secondary lysosomes, release of degraded material and recycling of themembrane. As an example of the normal degradative power of the macrophage, an adult individual has 5-1013 red blood cells of which 1/120 or 5-1011 are removed each day by splenic macrophages. In one year, splenic mononuclear phagocytize, eat and digest 2.7 kg of hemoglobin.a) Energy requirements. While pinocytosis is linear from 2°-38° phagocytosis fails to occur at temperaturesless than 18°. Phagocytosis is inhibited by glycolytic but not respiratory inhibitors, e. g. NaF, but not DNP. Theenergy for phagocytosis comes from ATP and creatine phosphate. The energy for pinocytosis requires both glycolysisand respiration, and can be inhibited by NaCN.
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NEW APPROACHES TO MACROPHAGE FUNCTION

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