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Study of Phagolysosome Biogenesis in Live Macrophages
Published on: March 11, 2014
Studies on phagocytosis in patients with acute bacterial infections
H H Simms1, M M Frank, T C Quinn
1Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Abstract:
Polymorphonuclear leukocytes (PMN) and monocytes from 20 patients with acute bacterial infections were examined for phagocytic function. PMN of patients expressed markedly enhanced phagocytosis as measured by the ingestion of erythrocyte (E)IgG and IgG/C3b-coated E. Phagocytosis of E coated with C3b alone was not seen, while low levels of ingestion of iC3b-E by patients' PMNs was noted. Monocytes from patients and controls expressed similar phagocytic activity in a fixed endpoint assay; however, the kinetics of phagocytosis by patients' monocytes was strikingly faster. Superoxide anion (O2.) and myeloperoxidase activities were similar to controls in PMN of four patients studied on day 1 of admission. PMN from two of three patients studied longitudinally showed an initial elevation in EIgG phagocytosis, which fell to normal levels by day 4, concomitantly with increased O2. generation and clinical improvement. Phagocytosis remained elevated in the third patient who did not clear his septicemia. Surface membrane FcRII, FcRIII, CR1, and CR3 were similar on patient and control PMN. In contrast, FcRI was increased on PMN of five of seven patients by monomeric IgG binding, and on two of two patients by monoclonal anti-FcRI binding. Thus, PMN and monocytes of patients with acute bacterial infections are either upregulated with regard to phagocytic function or are less susceptible to downregulation than are normal cells. This presumably would have a beneficial effect on host defenses during infection.
Insights
Polymorphonuclear leukocytes (PMN) and monocytes show enhanced phagocytic function during acute bacterial infections. This improved immune cell activity may bolster the body's defenses against pathogens.
Area of Science:
- Immunology
- Cell Biology
- Infectious Disease
Background:
- Acute bacterial infections trigger complex immune responses.
- Phagocytic cells, including polymorphonuclear leukocytes (PMN) and monocytes, are crucial for pathogen clearance.
- Understanding alterations in phagocytic function during infection is key to host defense mechanisms.
Purpose of the Study:
- To investigate the phagocytic function of PMN and monocytes in patients with acute bacterial infections.
- To compare the phagocytic activity and receptor expression of immune cells from infected patients versus healthy controls.
- To explore the correlation between phagocytic function, cellular activity, and clinical outcomes.
Main Methods:
- Collected blood samples from 20 patients with acute bacterial infections and healthy controls.
- Assessed phagocytosis of antibody (IgG) and complement (C3b, iC3b)-coated erythrocytes by PMN and monocytes.
- Measured superoxide anion (O2.) and myeloperoxidase activities in PMN.
- Analyzed surface membrane receptor expression (FcRI, FcRII, FcRIII, CR1, CR3) on PMN.
Main Results:
- Patients' PMN exhibited significantly enhanced phagocytosis of IgG-coated erythrocytes.
- Monocytes displayed faster phagocytosis kinetics in infected patients compared to controls.
- FcRI expression was increased on PMN from a majority of patients.
- Longitudinal studies showed phagocytic function normalization correlated with clinical improvement and increased O2. generation.
Conclusions:
- PMN and monocytes in patients with acute bacterial infections demonstrate upregulated phagocytic function.
- This enhanced immune cell activity likely contributes to improved host defense during infection.
- The findings suggest a beneficial role of heightened phagocytosis in combating bacterial pathogens.
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