The effect of unconjugated bilirubin on neutrophil polymorphs was studied in‐vitro by standard phagocytic and bactericidal assays. At concentrations attainable clinically, bilirubin was shown to inhibit both phagocytosis and killing of Staphylococcus aureus. These results suggest that jaundiced newboms may have an increased susceptibility to infection.

Background: Diabetes mellitus exacerbates immune dysfunction, leading to higher susceptibility to infections. This study investigated the effects of antibiotics on macrophage functions under high glucose conditions to mimic a diabetic context. Methods: Using murine macrophage cell line RAW 264.7, the present study evaluated the cytotoxicity, phagocytosis, bactericidal activity, and pro-inflammatory cytokine production after treatment with four antibiotics: oxytetracycline, ciprofloxacin, sulfamethoxazole–trimethoprim, and cefotaxime. Results: All antibiotics demonstrated no cytotoxicity across 1×–8× MIC concentrations. Hyperglycemia significantly impaired macrophage phagocytosis and bactericidal activity while inducing pro-inflammatory mediator markers, IL-1, IL-6, TNF-α, and iNOS. Only ciprofloxacin significantly improved phagocytic achieving levels comparable to the low glucose control. Treatments with ciprofloxacin, sulfamethoxazole–trimethoprim, and cefotaxime significantly enhanced bactericidal activity without altering the pro-inflammatory cytokine profile. Conclusions: These findings underscore the negative effect of high glucose on macrophage functions and suggest that ciprofloxacin may be a potential therapeutic option for diabetes-associated infections.

Virus infection of alveolar macrophages (AM) both in vivo and in vitro has been associated with a decreased ability of these cells to kill bacteria, together with enhanced production of metabolites of arachidonic acid. These metabolites, especially PGE2, may be inhibitory to some phagocyte functions. Primary cultures of bovine AM obtained by bronchoalveolar lavage of normal cattle were infected in vitro with parainfluenza-3 (PI3 virus) virus. Killing of Staphylococcus epidermidis by AM was determined on days 1-4 post-infection (p.i.) PI3 virus-infected AM killed significantly fewer bacteria on day 4 p.i. compared to uninfected controls (12.1 ± 1.3% infected vs. 52.7 ± 7.2% controls, P ≤ 0.05). Bacterial killing by virus-infected AM, but not control AM, was significantly enhanced on day 4 p.i. by addition of cyclooxygenase inhibitors 1 hr prior to bactericidal assay (28.0 ± 4.5% indomethacin, 36.0 ± 4.1% mefenamic acid, 38.6 ± 7.3% piroxicam, 37.0 ± 6.4% NDGA, 44.9 ± 7.7% ETYA, P ≤ 0.05). Phagocytosis of opsonized sheep erythrocytes and superoxide generation by virus-infected AM were not significantly increased by cyclooxygenase inhibition. Phagosome-lysosome fusion was severely impaired in virus-infected AM. Pretreatment of virus-infected AM with indomethacin significantly enhanced the percentage of cell expressing fusion activity. This data suggests that in vitro bactericidal dysfunction associated with virus infection of AM is partially the result of enhanced production of prostaglandins or thromboxane by AM and/or an abnormal response to normal levels of endogenously produced cyclooxygenase metabolites. The data further indicate the presence of cyclooxygenase sensitive (phagosome-lysosome fusion) and insensitive (phagocytic) components of virus-induced bactericidal dysfunction in AM.

Abstract The phagocytic and bactericidal activities of neutrophil granulocytes from 5 patients with early acute myelomonocytic or myeloblasts leukaemia and 5 controls have been examined. In each patient the bactericidal activity was lower than in any control and the neutrophil dysfunction was demonstrated before leukaemia could be diagnosed from clinical and haematological findings. During periods of remission, the bactericidal activity was normal. Results of neutrophil granulocyte function studies may be a significant aid in the early diagnosis of acute myelomonocytic and myeloblasts leukaemia.

Bone defects arising from trauma and tumors present a potential risk of infection and compromise host immune function. Within a dysfunctional microenvironment, the uncontrolled breeding of bacteria and persistent chronic inflammation exacerbate bone loss, impeding bone regeneration and repair. Macrophages function as specialized phagocytes within the immune microenvironment and the orchestrated role of distinct phenotypes during regeneration has attracted significant attention. The M1 phenotype exhibits antimicrobial activities to eliminate bacterial threats, while the M2 phenotype secretes anti‐inflammatory mediators to fine‐tune the immune microenvironment. Here, a biphasic delivery system consisting of a photothermal agent (graphene oxide, GO) coated and an immune modulator (urolithin A, UA) encapsulated in coaxial electrospun nanofibers with a dynamic regulation function of macrophage behavior is designed. It is observed that the GO coating exhibited remarkable photothermal performance within the near‐infrared window, affecting the phagocytic activity of macrophage subsets in an integrin‐RhoA‐ROCK1 dependent manner. The sustained release of UA from the core layer induced a phenotypic switch by downregulating TNF signaling and upregulating TGF signaling. This system also demonstrated a promotion of bone regeneration in vivo. Overall, this strategy achieved sequential regulation of macrophage phenotypes, effectively preventing infection and fostering bone tissue regeneration.

We hypothesized that neutrophil function in tumour‐bearing dogs is negatively impacted by chemotherapy. Flow cytometric techniques were used to assess neutrophil oxidative burst and phagocytic activities at baseline, 7 and 21 days after induction chemotherapy in 20 dogs with lymphoma. Dogs had a lower percentage of neutrophils exhibiting oxidative burst activity after stimulation with Escherichia coli (day 7; P = 0.009) and phorbol 12‐myristate 13‐acetate (PMA) (days 7 and 21; P = 0.0003 and P = 0.01, respectively), compared with healthy controls. From day 0 to 7, the percentage of neutrophils exhibiting oxidative burst activity decreased after stimulation with E. coli (P = 0.016) and PMA (P = 0.0006). Induction chemotherapy suppresses the percentage of neutrophils capable of oxidative burst in dogs with lymphoma, with improvement in phagocytic activity over time (P = 0.03). The impact of neutrophil dysfunction on incidence and severity of sepsis in dogs receiving chemotherapy should be investigated.

The bactericidal defect of CGD PMNs has been partially corrected in previous studies relying on the co-phagocytosis of bacteria and of either glucose oxidase (GO)-coated latex particles or GO-containing liposomes. We investigated the effect of opsonization of bacteria with an IgG-GO conjugate upon the bactericidal activity of CGD PMNs and monocytes (MC). Anti-staphylococcal rabbit IgG was prepared and conjugated to GO by diethylmalonimidation. The conjugate (final concentration of IgG: 2.0 mg/ml) was used to opsonize bacteria which were then ingested by PMNs or MCs of female CGD carriers. In control preparations IgG alone was used as opsonin. After 120 minutes of incubation with CGD PMNs, the number of surviving intracellular bacteria decreased from a mean of 42.3% (opsonin: IgG) to 17.7% (opsonin: IgG-GO conjugate). In MCs of CGD carriers the number of intracellular bacteria decreased by 45%. In PMN-free preparation the IgG-GO conjugate displayed negligible bactericidal activity. The bactericidal defect of CGD phagocytic cells can be successfully corrected by the intracellular introduction of an IgG-GO conjugate. Furthermore, such restoration of bactericidal activity may be enhanced by the close proximity between the bacteria and the hydrogen peroxide-generating opsonin.

Chronic inflammation of the lung, as a consequence of persistent bacterial infections by several opportunistic pathogens represents the main cause of mortality and morbidity in cystic fibrosis (CF) patients. Mechanisms leading to increased susceptibility to bacterial infections in CF are not completely known, although the involvement of cystic fibrosis transmembrane conductance regulator (CFTR) in microbicidal functions of macrophages is emerging. Tissue macrophages differentiate in situ from infiltrating monocytes, additionally, mature macrophages from different tissues, although having a number of common activities, exhibit variation in some molecular and cellular functions. In order to highlight possible intrinsic macrophage defects due to CFTR dysfunction, we have focused our attention on in vitro differentiated macrophages from human peripheral blood monocytes. Here we report on the contribution of CFTR in the bactericidal activity against Pseudomonas aeruginosa of monocyte derived human macrophages. At first, by real time PCR, immunofluorescence and patch clamp recordings we demonstrated that CFTR is expressed and is mainly localized to surface plasma membranes of human monocyte derived macrophages (MDM) where it acts as a cAMP-dependent chloride channel. Next, we evaluated the bactericidal activity of P. aeruginosa infected macrophages from healthy donors and CF patients by antibiotic protection assays. Our results demonstrate that control and CF macrophages do not differ in the phagocytic activity when infected with P. aeruginosa . Rather, although a reduction of intracellular live bacteria was detected in both non-CF and CF cells, the percentage of surviving bacteria was significantly higher in CF cells. These findings further support the role of CFTR in the fundamental functions of innate immune cells including eradication of bacterial infections by macrophages.