CD64 antigen - an overview (2023)

auxiliary studies

Morphological properties of hyalocytes

Morphological studies using light and electron microscopy show that hyalocytes vary in shape from oval to fusiform or stellate, and that hyalocytes possess lysosomes, mitochondria, ribosomes, and micropinocytic vesicles with numerous microvilli on their surface, indicating that hyalocytes are morphologically very similar are among the so-called macrophages. Therefore, hyalocytes are considered to belong to the monocyte/macrophage lineage (Figure 1(b)).

Immunocytochemical analysis indicates that hyalocytes possess antigenic determinants that react with antibodies directed against CD45 (leukocyte common antigen), CD64 (Fc receptor I), CD11a (leukocyte function antigen-1), histocompatibility complex class II antigens (MHC ) and S100 protein. The presence of CD45, which is selectively expressed on all hematopoietic cells except mature erythroid cells, and CD11a, which is present on virtually all leukocytes, strongly suggests that the hyalocytes are derived from a leukocyte cell lineage. In addition, Fc receptor I is the specific IgG receptor that is constitutively only expressed by monocytes and tissue macrophages. The expression of MHC class II antigens and S100 protein, while not exclusive to the monocyte/macrophage lineage, is consistent with this cellular origin.

Although hyalocytes do not react with CD11b, CD11c, or CD14, these antigenic determinants are differentially expressed on tissue macrophages. They differ from other cells of the mononuclear phagocytic system in that they lack the immunocytochemically detectable CD68 antigen, an epitope that is highly expressed on peripheral blood monocytes and macrophages in virtually all tissues. In addition, antigens typically associated with epithelial cells (cytokeratin and epithelial membrane antigen), fibroblasts (prolyl-4-hydroxylase and vimentin), endothelial cells (CD31 and von Willebrand factor), glial cells (glial fibrillary acidic protein: GFAP) and neuronal cells (neuron-specific enolase) cells and RPE cells and Muller cells (cellular retinaldehyde-binding protein) are not present in hyalocytes.

In addition, further immunophenotypic analysis showed that the majority (90%) of the hyalocytes were positive to the ED2 antibody, which recognizes membrane and cytoplasmic antigens of tissue macrophages, and some (15%) hyalocytes were positive to the ED1 antibody, d recognizes an antigen. in monocytes and in most macrophages, free and fixed. Only 5% of the hyalocytes stained positive for both ED1 and ED2. Antibodies directed against ED1, which have the characteristic phenotype of monocyte-derived macrophages, label only a small fraction of hyalocytes. Antibodies directed against ED2, which are typically associated with hyalocytes, illustrate that vitreous hyalocytes have the characteristic phenotype of tissue macrophages.

1.1 Pharmacological conditioning of immune responses

The study of conditioned pharmacological effects began with the discovery of conditioned immune responses. The first reports of this phenomenon date back to the 1920s or even earlier. In the years that followed, the conditioned reactions of the immune system were mainly investigated in animal experiments (cfPacheco-Lopez et al., 2007). In an exemplary human study using a conditioning design with multiple acquisition and memory sessions,Buske-Kirschbaum et al. (1992)showed that the increase in natural killer cell activity caused by the administration of epinephrine could be conditioned. In the acquisition phase of their experiment, they combined a sweet straw (CS) with the 0.2 mg injection of epinephrine (UCS). In the recall phase, when CS was co-administered with a placebo injection, a conditioned increase in natural killer cell (NKCA) activity was observed. The results of this experiment could only be partially replicated (Kirschbaum et al., 1992). However, another study with a discriminatory conditioning design found more evidence of the possibility of conditioning the NKCA with epinephrine and a taste CS. In this study, administration of one CS, the CS+ (Sorbet Candy and White Noise), was followed by an injection of the UCS (0.2 mg epinephrine), while administration of another CS, the CS− (Herbal Candy with Sound -specific effect), no treatment followed. In the evocation phase, CS+ exposure resulted in an increase in NKCA, while CS− exposure had no effect on NKCA (Buske-Kirschbaum, Kirschbaum, Stierle, Jabaij y Hellhammer, 1994). Taken together, these studies provide relatively strong evidence that NKCA may be pharmacologically related in humans.

There is also evidence that other pro-inflammatory immune parameters may be conditioned. One study found higher levels of quinolinic acid and neopterin and higherCD64-AntigenExpression following pairing of recombinant human interferon gamma (rhIFN-γ, UCS) with propylene glycol (CS) flavor in an intermittent treatment design (Largoet al., 1999). In another study with a single study conditioning design (illustration 1, Part 1), an injection of IFNβ-1a (UCS) was combined with administration of a characteristically flavored beverage. When the drink was administered 8 days later in combination with a placebo injection, no conditioned responses were observed (Göbel et al., 2005). Similarly, a study using the same conditioning paradigm in a trial of UCS and the same distinctively flavored drink also found no conditioned immunological effects (Grigoleite et al., 2012). Taken together, these studies suggest that it is possible to condition pro-inflammatory immune responses by combining immunostimulatory drugs with taste stimuli, but more evidence is needed to support these findings. Various conditioning designs can be used to study these effects, although conditioning in a single experiment does not appear to be effective in conditioning pro-inflammatory immune responses.

The pharmacological conditioning of immune responses towards immunosuppression was also examined. In most studies, oral administration of the immunosuppressive drug cyclosporine A (CsA, UCS) was combined with a distinctly flavored drink (CS) in the procurement phase. When CS was co-administered with placebo during recall, it consistently resulted in a conditional decrease in production of the cytokine interleukin 2 (Albring et al., 2014;Göbel et al., 2002;Ober et al., 2012;Wirth et al., 2011). Some studies also found a conditional reduction in IFN-γ production (Göbel et al., 2002;Wirth et al., 2011) and lymphocyte proliferation (Göbel et al., 2002). All of these are indicators of conditioned immunosuppression. Through inter-study variation in the number of recall sessions, we found evidence that these conditioned immunosuppressive responses may not manifest for more than one recall session (Albring et al., 2012). Once conditioned responses are established, they are relatively stable, having only been shown to subside after 14 evocations (Albring et al., 2014). In addition, this type of conditioning can potentiate the effect of a subtherapeutic dose of CsA to clinically relevant levels (Albring et al., 2014), a finding that points to possible possibilities for clinical applications based on conditioned pharmacological effects.

Conditioned allergic reactions provide further examples of conditioned drug effects. In two studies, allergens (UCS) were administered via a nasal spray containing a distinctive odor (CS) (Barrett et al., 2000;Gauci et al., 1994). When the CS was used alone (nasal spray with the smell but without the allergen), it caused histamine elevations (Barrett et al., 2000) and tryptase (Gauci et al., 1994) were found in nasal discharge. Interestingly, in contrast to studies on conditioned immune stimulation, conditioned responses appeared even after a single acquisition (single-trial conditioning) and tended to be extinct.Barrett et al., 2000). However, the conditioned responses increased with more acquisition attempts (Barrett et al., 2000). In another study, dermal allergen application (UCS) was combined with visual CS (the color of the vial containing the allergen) during the acquisition phase. No conditioned responses were found in this experiment (Booth, Petrie and Brook, 1995). Although allergen conditioning studies have found effects on histamine and tryptase involved in allergic reactions, no effects on allergic symptoms (i.e. nasal congestion or sneezing) have been found. However,Göbelet et al. (2008)found that allergic symptoms can be controlled if the antiallergic effects are conditioned. In this study, administration of an antiallergic drug (desloratadine, UCS) during the acquisition phase was combined with a characteristically flavored drink (CS). When the drink was later administered in combination with a placebo, a conditioned decrease in basophil activation, a reduced response to a skin prick test, and lower symptom scores were found. However, in an attempt to replicate these promising results in another study, the antiallergic effects of the conditioning did not outperform those of the placebo group, but both groups improved in terms of symptoms compared to a natural history group. This finding suggests that both conditioning and expectancy-based effects may play a role (Jokes et al., 2013). In summary, there are at least preliminary indications that pharmacological conditioning of immune responses in the direction of immunostimulation and immunosuppression as well as allergic reactions are possible in the laboratory.

5.2 Intestinal monocytes and macrophages in recognitionopen

Gut macrophages play an important role in the host anti-inflammatory response and in maintaining local homeostasis. Macrophages reside in the intestinal lamina propria where they act as innate effector cells. Intestinal macrophages express theCD64-Antigenand are constantly being differentiated by blood monocytes (Cerovic et al., 2014). in oneC. albicansinfection, neutrophils and monocytes are superior to macrophages in terms of their microbial activity. However, macrophages are still effective at killingC. albicansunder both aerobic and anaerobic conditions. Monocytes lose their microbial capacity by differentiating into macrophages.in-vitro. This loss of microbial activity has been shown to be related to the loss of the enzyme myeloperoxidase and a reduced ability to produce hydroxyl radicals.Sasada et al., 1987). However, macrophages that adhere to type I collagen matrices can increase the host's ability to kill ingested Candida by enhancing fusion between phagosomes and yeast-containing lysosomes.Newmanet al., 2005). When answering aC. albicansInfection, macrophages differentiate into a pro-inflammatory subtype (M1, classically activated macrophages) or an anti-inflammatory subtype (M2, alternatively activated macrophages). Changing from M1 to M2 can helpopenPathogenicity by reducing the immune response and thus allowing fungal colonization. Alternatively, the host's immune system may try to eliminate themc.albicans,and limit the infection damage (Reales-Calderón et al., 2014). CLRs form the main PRR of macrophages. Activation of Dectin-1 and Dectin-2 leads to spleen tyrosine kinase (Syk)-dependent formation of a CARD9-Bcl-10-MALT1 complex and recruitment and activation of MALT1-Caspase8-ASC-containing inflammasomes that mediate IL- 1β processing during aC. albicansInfection (Gringhuis et al., 2012). The Dectin-1 dependent pathway is required for the generation of ROS by NADPH oxidase in fungal phagosomes.Tam et al., 2014).C. albicansit is able to kill and escape from macrophages. Next to,C. albicansHyphae cells can induce NLRP3-mediated pyroptosis in macrophages and disrupt their cell integrity.Wellingtonet al., 2013).

3.4 CD64

Neutrophils can express three classes of IgG receptors: FcγI receptor (FcγRI), which is the high-affinity receptor for monomeric IgG1 and IgG3 and also binds aggregated IgG; The Fcγ II receptor (FcγRII) and Fcγ III receptor (FcγRIII), which bind IgG but with low affinity (Nuutila et al., 2007). These receptors are recognized by the monoclonal antibodies CD64 (FcγRI), CD32 (FcγRII) and CD16 (FcγRIII) (Zola et al., 2007). CD64 is expressed at very low levels on resting mature neutrophils. After activation of neutrophils, it is tightly regulated by the pro-inflammatory cytokines IFN-γ and granulocyte colony-stimulating factor (G-CSF), which are produced during infection or endotoxin exposure.Van Der Meer et al., 2007). The other two Fcγ receptors are constitutively expressed and also upregulated during neutrophil activation. However, the differences in expression between resting and activated neutrophils are much larger for CD64. therefore, theCD64-Antigenis the most useful candidate marker for bloodstream infections (Davis et al., 2006;Davis, 2005). Monocytes also express CD64 and upregulate this receptor during activation. The longitudinal patterns of CD64 upregulation on monocytes and neutrophils are strikingly similar, although the change in CD64 expression is considerably greater for neutrophils.Barthet al., 2001).

The CD64 neutrophil has many properties that make it clinically useful as a marker for sepsis. JJ Hoffmann verified the reasons as follows (Hoffmann, 2009). First, CD64 directly reflects the physiological events of the inflammatory response to invading microorganisms. Second, the level of expression of CD64 in resting neutrophils is quite low. However, after activation, it can increase by 5-10 times (Songet al., 2008), which allows for a good distinction between health and disease. Third, neutrophilic CD64 rapidly becomes positive: CD64 expression is a biphasic pattern, increasing at 2 hours and more significantly at 6 hours. After the stimulation was removed, CD64 levels fell within 48 hours (Van Der Meer et al., 2007). Furthermore, neutrophil CD64 upregulation is specific to bloodstream infections, and few other disorders are associated with CD64 upregulation. Finally, the CD64 neutrophil assay is relatively simple and rapid. These recommendations should be accepted as a general reference standard for a diagnostic biomarker.

But there is a difference between two test methods on CD64. A report showed that when using flow cytometry and Leuko64-Kit™ to test CD64 levels, SROC values ​​were 0.95 and 0.85, respectively (Page= 0.013). In addition, the costly analysis of flow cytometry prevents its clinical use (Larsen and Petersen, 2017). Based on the meta-analysis, Luo Q et al. suggest that the CD64 neutrophil is not a perfect marker for sepsis (Luo et al., 2018). Morsy et al. reported that the sensitivity of CD64 in diagnosing local infection was significantly lower (Morsyet al., 2008). Because sepsis is a complex and dynamic syndrome and no single test is sensitive and specific enough to detect sepsis (Luo et al., 2018). To date, scientists have not found a biomarker with sufficient sensitivity and specificity to diagnose sepsis. However, a growing number of studies have shown that combinations of different markers are a useful approach to improve the accuracy of sepsis diagnosis.Luo et al., 2018). For example Gibot et al. indicated that a combination of CD64 neutrophils, sTREM-1 and PCT could have much better diagnostic performance for sepsis (Gibot et al.).