Abstract
Objective Neutrophils are key effector cells of the innate immune system. They recognize antigens through membrane receptors, which are expressed during their maturation and activation. Neutrophils express FcγRII (CD32), FcγRIII (CD16), and FcγRI (CD64) after being activated by different factors such as cytokines and bacterial products. These receptors are involved with phagocytosis of IgG-opsonized microbes and enhance defense mechanisms. Based on that, our study seeks to compare the expression of FcγRII, FcγRIII, FcγRI, and CD11b on neutrophils from elderly and young subjects and their expression after in vitro activation with cytokines and LPS.Methodology Neutrophils were isolated from human peripheral blood and from mice bone marrow by density gradient. After isolation, FCγRs expression was immediately analyzed by flow cytometry or after in vitro stimulation.Results In freshly isolated cells, the percentage of FcγRIIIb+ and CD11b+ neutrophils were higher in samples from young individuals; FcγRIIIa expression was more prominent on aged neutrophils; FcγRIA expression was similar in all samples analyzed. Exposure to CXCL8 and LPS resulted in a higher percentage of FcγRIa+ neutrophils on elderly individuals’ samples but lower when compared with neutrophils from young donors. We observed that LPS caused an increase in FcγRIIa expression on aging human neutrophils. In contrast, FcγRIIIb expression in response to CXCL8 and LPS stimulation was not altered in the four groups. CD11b expression was lower in neutrophils from elderly individuals even in response to LPS and CXCL8. In mice, we observed differences only regarding CD11b expression, which was increased on aged neutrophils. LPS exposure caused an increase in all FcγRs.Conclusions Our results suggest that, in humans, the overall pattern of FcγR expression and integrin CD11b are altered during aging and immunosenescence might contribute to age-related infection.
Highlights
IntroductionNeutrophils are the first inflammatory cell to infiltrate inflamed or infected tissue; they are recognized as major components of the host’s first line of defense. They immediately migrate to the infected site, become activated, and initiate a cascade of defense mechanisms that effectively contribute to the development of the adaptive immune response. Several cytokines, such as CXCL8 and TNF, have been described as chemoattractants and activators for neutrophils. Basal levels of CXCL8, the most neutrophil attractant and activator, are detected in the peripheral blood of healthy subjects, but certain diseases can cause CXCL8 deregulation and affect neutrophil function.5,6Neutrophils motility and activity rely on the expression of specialized membrane molecules, which allows them to adhere and transmigrate through the endothelium as well as to recognize and phagocytize opsonized microorganisms. Among them, the family of Fc gamma receptors for IgG (FcγRs) plays an essential role during neutrophils activation and function
In freshly isolated cells, the percentage of FcγRIIIb+ and CD11b+ neutrophils were higher in samples from young individuals; FcγRIIIa expression was more prominent on aged neutrophils; FcγRIA expression was similar in all samples analyzed
Since CD11b is essential for neutrophils extravasation and recruitment;20 we compared its expression on neutrophils from elderly and young individuals and our results showed that the frequency of CD66+/CD11b+ human neutrophils decreases with age (Figure 1F)
Summary
Neutrophils are the first inflammatory cell to infiltrate inflamed or infected tissue; they are recognized as major components of the host’s first line of defense. They immediately migrate to the infected site, become activated, and initiate a cascade of defense mechanisms that effectively contribute to the development of the adaptive immune response. Several cytokines, such as CXCL8 and TNF, have been described as chemoattractants and activators for neutrophils. Basal levels of CXCL8, the most neutrophil attractant and activator, are detected in the peripheral blood of healthy subjects, but certain diseases can cause CXCL8 deregulation and affect neutrophil function.5,6Neutrophils motility and activity rely on the expression of specialized membrane molecules, which allows them to adhere and transmigrate through the endothelium as well as to recognize and phagocytize opsonized microorganisms. Among them, the family of Fc gamma receptors for IgG (FcγRs) plays an essential role during neutrophils activation and function. Neutrophils are the first inflammatory cell to infiltrate inflamed or infected tissue; they are recognized as major components of the host’s first line of defense.. Neutrophils are the first inflammatory cell to infiltrate inflamed or infected tissue; they are recognized as major components of the host’s first line of defense.1 They immediately migrate to the infected site, become activated, and initiate a cascade of defense mechanisms that effectively contribute to the development of the adaptive immune response.. They immediately migrate to the infected site, become activated, and initiate a cascade of defense mechanisms that effectively contribute to the development of the adaptive immune response.2,3 Several cytokines, such as CXCL8 and TNF, have been described as chemoattractants and activators for neutrophils.. FcγRs mediate antibody-dependent cellular cytotoxicity (ADCC) and the phagocytosis of opsonized invading pathogens, and elicit neutrophil recruitment. The most well-studied FcγRs are the ones that belong to the family of type I FcγRs. the FcγRIIIb (CD16) is the most abundant FcγR; the FcγRIIa (CD32) is an activating-type Fc receptor and is the second most expressed FcγR; and the less abundant FcγR is the high-affinity receptor FcγRIa (CD64), which binds to IgG2a (mice) or IgG1 and IgG3 (humans).
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