Rapid Decrease of CD16 (FcγRIII) Expression on Heat‐Shocked Neutrophils and Their Recognition by Macrophages

Abstract

Accumulation of neutrophils in the site of inflammation is a typical mechanism of innate immunity. The accumulated neutrophils are exposed to stressogenic factors usually associated with inflammation. Here, we studied response of human peripheral blood neutrophils subjected to short, febrile-range heat stress. We show that 90 min heat stress slowed down the spontaneous apoptosis of neutrophils. In the absence of typical markers of apoptosis the heat-shocked neutrophils induced antiinflammatory effect in human monocyte-derived macrophages (hMDMs), yet without being engulfed. Importantly, the expression of FcγRIII (CD16) was sharply reduced. Surprisingly, concentration of the soluble CD16 did not change in heat-shocked neutrophil supernates indicating that the reduction of the cell surface CD16 was achieved mainly by inhibition of fresh CD16 delivery. Inhibitors of 90 kDa heat shock protein (HSP90), a molecular chaperone found in membrane platforms together with CD16 and CD11b, significantly increased the observed effects caused by heat shock. The presented data suggest a novel systemic aspect of increased temperature which relies on immediate modification by heat of a neutrophil molecular pattern. This effect precedes cell death and may be beneficial in the initial phase of inflammation providing a nonphlogistic signal to macrophages before it comes from apoptotic cells.

Heat dissipation does not suppress an immune response in laboratory mice divergently selected for basal metabolic rate (BMR)

“…This result is consistent with other studies that have demonstrated that heat stress increased, or did not change, parameters of non-specific immunity, such as the percentage of neutrophils, monocytes or eosinophils, the anti-inflammatory effect of neutrophils, the neutrophil response to chemoattractants, respiratory burns of neutrophils and natural killer cell cytotoxicity (e.g. Ostberg et al, 2005;Sutherland et al, 2006;Bzowska et al, 2011). In addition, changes in blood parameters were similar to those observed in our previous study, in which mice from selected line types were subjected to another metabolic challenge: a 30% restriction in food intake (Ksiazėk and Konarzewski, 2012).…”

Silver nanoparticles rapidly induce atypical human neutrophil cell death by a process involving inflammatory caspases and reactive oxygen species and induce neutrophil extracellular traps release upon cell adhesion

“…Of note, we have previously reported that a crude hydroalcoholic extract from the Brazilian plant Esenbeckia leiocarpa was found to induce atypical PMN apoptosis as assessed by cytology and by flow cytometry using FITC-annexin-V, without inducing CD16 shedding after 22 h of treatment whereas, in parallel, the plant lectin Viscum album agglutinin-I was found to induce apoptosis and inducing CD16 shedding [41]. In contrast, a rapid decrease of CD16 expression was reported after 90 min of heat-shock treatment in human PMNs, delaying their spontaneous apoptotic rate [12]. Putting these above studies together, with the one present here, clearly indicated that CD16 shedding does not always correlate with apoptosis; this is why we have next investigated if AgNP 15 -induced cell death could be regulated by different caspases.…”

“…Under physiological conditions, these cells have a very short lifespan, remaining for only 12-24 h in circulation, when they undergo spontaneous apoptosis, a process known to regulate the number of neutrophils relatively constant under normal circumstance. In addition, apoptotic neutrophils are promptly removed by macrophages during the neutrophil clearance by inflammatory macrophages in the liver, spleen, and/or bone marrow [12][13][14]. On the other hand, in the presence of inflammatory stimuli, activated PMNs may remain in circulation for several days.…”

NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17)

“…Soluble CD16 was measured by a sandwich enzymelinked immunosorbent assay (ELISA) as previously described. 26 Briefly, flatbottom, 96-well polystyrene microplates were pre-coated with 100 mL of 10 mg/mL anti-CD16 (clone 3G8) diluted in PBS and incubated overnight at 4°C. Plates were washed with PBS containing 0.05% Tween-20 and blocked with 300 mL PBS containing 2% BSA at 37°C for 1 hour.…”