**2. Neutrophil granulocyte receptors**

Cell populations and subpopulations of NG show a high degree of plasticity and functional heterogeneity depending on the characteristics of the course of physiological or pathological scenarios of the immune response, which, first of all, is due to potent receptor equipment. The membrane complex of NG expresses adhesion molecules, receptors for different ligands: cytokines, immunoglobulins, other cell membrane molecules, etc. NGs are capable to express MHC-1, selectins (CD62L), selectin receptors (CD162 (PSGL-1)), integrins (CD18 (β2-integrin), CD11a (LFA-1), CD11b (CR3), CD11c (CR4), CD11d), integrin receptors (ICAM receptors for β2-integrins - ICAM-1 (CD50), ICAM-3 (CD54). NG expresses receptors for chemoattractants (PFPR and FPLR for fMLP), receptors for chemokines (CXCR1, CXC2, CCR1), FcR receptors (CD16 (FcγRIII), CD32 (FcγRII), CD64 (FcγRI), CD89 (FcαRI), FcεR), receptors for complement components (CR1 (CD35), CR3 (CD11b), CR4 (CD11c), C5aR, C3aR, C5L2), receptor for LPS and endotoxins (CD14), cell adhesion receptor (CD15). NG receptors are involved in binding bacteria, in angiogenesis and apoptosis (CD17), in cell proliferation and differentiation (CD24), in PAMP recognition (TLR 1, 2, 4-10; NOD - receptors). In addition, on NG membrane there is a costimulatory receptor for B- lymphocytes (CD28), apoptosis activation/induction receptor (CD95), IL-2 receptor (CD25), which is NG activation marker; there are also molecules that determine the ability of NG to be APC (CD40, CD80, CD86, MHC II). NGs have multiple receptors for cytokines (IL-8, TNFα, IL-1, IL-2, IL-15, IL-17, IFNα, IFNγ, G-CSF, GM-CSF, etc.), hormones, neuropeptides, histamine, and kinases. The recently revealed expression of TCR-like (TCRL, TCRαβ) receptors on NG membrane, present throughout the life of a person and decreasing in old age, opens up new, previously unknown immune mechanisms for the functioning of NG [2] (**Figure 1**).

NGs are equipped with receptors that recognize endogenous molecules of "danger" alarms or danger-associated molecular patterns (DAMPs)—extracellular ATP, fragments of the extracellular matrix, heat shock proteins, nucleic acids (DNA and RNA fragments of its own cells), nuclear protein HMGB-1, and others—through which activation of the cell takes place and its inclusion in the inflammation reaction [3]. It has been established that the initiation of apoptosis of NG in clinically healthy individuals is under the influence of TNFα, sTRAIL, and IL-4 ligand [4]. Recently, new ways of activating the NG signal via ITAM/Syk-CARD9 have been described in the interaction of β-glycans with dectin-1, which triggers the synthesis of the cytokine IL-23 inducing the formation of Th17 cells [5]. NG receptor pool is located on intracellular membrane of secretory vesicles, gelatinase and specific granules, these receptors are translocated to surface membrane of NG only under the action of inducing stimuli [6]. Thus, the membrane expression of NG not only reflects the

**45**

*Remodeling of Phenotype CD16+*

**granulocytes**

**Figure 1.**

*DOI: http://dx.doi.org/10.5772/intechopen.81631*

*Surface membrane receptors of neutrophilic granulocytes.*

*CD11b+*

processes occurring during the life cycle of the cell but also allows us to evaluate the functional priming by reorganizing the surface cytoplasmic membrane of NG.

The study of the subpopulations of NG presents a new approach to the determination of functional activity of NG, allowing to assess the adequacy of the inclusion of NG in the implementation of the immune response, as well as to diagnose and predict the outcome of the disease. It is known that various phenotypic profiles and the level of equipment with surface receptors are associated with morphological features and determine the functional potential of NG-cytokine production, transendothelial migration, intracellular and extracellular killing, and formation of NET [7–9]. The existence of a sufficiently large number of NG subpopulations with different possibilities is demonstrated. NGs that receive complex cytokine influences not only acquire new features but also undergo different stages of activation and differentiation while expressing MHCII antigens, CD80, CD86, ICAM-1, and LFA-1 [7, 10, 11]. It has been shown that inducing cytokine stimuli differentiates NG in a unique hybrid subpopulation with dual phenotypic and functional properties characteristic of both NG and dendritic cells (DC) involved in innate and adaptive immune responses [12]. We have identified in our earlier works the following subpopulations of NG: regulatory; suppressor; pro-inflammatory, initiating inflammatory reaction; inflammatory with a positive microbicidal potential (antibacterial, antiviral, antifungal); inflammatory with negative cytotoxic potential, "aggressive"; anti-inflammatory, regulating inflammation regression; antineoplastic, TAN1; and pro-tumor, TAN2 and hybrid [13]. Phagocytic and microbicidal function and virucidal activity of NG are directly dependent on phenotypic features: the number and density of such expressed receptors as CD11b/CD18, CD10, CD15, CD16, CD32, CD64, CD35, etc. [6]. Expression on NG membrane of CD32 and CD16 is important

**3. Phenotypic profile and functional features of neutrophil** 

 *Neutrophilic Granulocytes in Acute Viral and Acute…*

*Remodeling of Phenotype CD16<sup>+</sup> CD11b+ Neutrophilic Granulocytes in Acute Viral and Acute… DOI: http://dx.doi.org/10.5772/intechopen.81631*

**Figure 1.** *Surface membrane receptors of neutrophilic granulocytes.*

processes occurring during the life cycle of the cell but also allows us to evaluate the functional priming by reorganizing the surface cytoplasmic membrane of NG.
