Airways exposure of bacterial superantigen SEB enhances bone marrow eosinophil population and facilitates its egress to blood and lung tissue.

BACKGROUND: Differentiation of bone marrow eosinophils (BM-EO) and its trafficking to peripheral blood and respiratory mucosa are a hallmark of inflammatory diseases. Staphylococcal enterotoxin B (SEB) has been shown to aggravate airways eosinophilic inflammation. This study aimed to investigate the effects of mouse airways SEB exposure on BM-EO population, as well as its adhesive properties and release of cytokines/chemokines that orchestrate BM-EO trafficking to lungs. METHODS: Male BALB/c mice were intranasally exposed to SEB (1 µg), and at 4, 16, 24 and 48 h thereafter, bone marrow (BM), circulating blood and bronchoalveolar lavage (BAL) fluid were collected. Levels of cytokines/chemokines and expressions of VLA-4 and CCR3 in BM were evaluated. Adhesion of BM to ICAM-1 and VCAM-1 were also evaluated. RESULTS: SEB exposure promoted a marked eosinophil influx to BAL at 16 and 24 h after exposure, which was accompanied by significant increases in counts of immature (16 h) and mature (4 to 48 h) forms of eosinophil in BM, along with blood eosinophilia (16 h). In BM, higher levels of eotaxin, IL-5, IL-4, IL-3 and IL-7 were detected at 16 to 48 h. SEB also significantly increased CCR3 expression and calcium levels in BM-EO, and enhanced the cell adhesion to ICAM-1 (24 h) and ICAM-1 (48 h). CONCLUSION: Airways SEB exposure increases the number of eosinophils in BM by mechanisms involving a network of cytokine and chemokine release, facilitating the BM-EO adhesion to ICAM-1 and VCAM-1 to gain access to the peripheral blood and lung tissues.

Airway exposure to Staphylococcal enterotoxin type B (SEB) enhances the number and activity of bone marrow neutrophils via the release of multiple cytokines.

BACKGROUND: The lung infections by Staphylococcus aureus are strongly associated with its ability to produce enterotoxins. However, little is known about the mechanisms underlying trafficking of bone marrow (BM) neutrophils during airway inflammation induced by Staphylococcal enterotoxin B (SEB). We therefore aimed to investigate the effects of mouse airways SEB exposure on BM neutrophil counts and its adhesive properties as well as on the release of cytokines/chemokines that orchestrate BM neutrophils trafficking to lung tissue. METHODS: Male BALB/c mice were intranasally exposed to SEB (1 µg), and at 4, 16 and 24 h thereafter, BM, circulating blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected. BM neutrophils adhesion, MAC-1 and LFA1-α expressions (by flow cytometry) as well as measurement of cytokine and/or chemokines levels were assayed after SEB-airway exposure. RESULTS: Prior exposure to SEB promoted a marked influx of neutrophils to BAL and lung tissue, which was accompanied by increased counts of BM immature neutrophils and blood neutrophilia. BM neutrophil expressions of LFA1-α and MAC-1 were unchanged by SEB exposure whereas a significant enhancement of adhesion properties to VCAM-1 was observed. The early phase of airway SEB exposure was accompanied by high levels of GM-CSF, G-CSF, IFN-γ, TNF-α and KC/CXCL1, while the latter phase by the equilibrated actions of SDF1-α and MIP-2. CONCLUSION: Mouse airways exposure to SEB induces BM cytokines/chemokines release and their integrated actions enhance the adhesion of BM neutrophils leading to acute lung injury.

Staphylococcal enterotoxin A regulates bone marrow granulocyte trafficking during pulmonary inflammatory disease in mice.

Pulmonary neutrophil infiltration produced by Staphylococcal enterotoxin A (SEA) airway exposure is accompanied by marked granulocyte accumulation in bone marrow (BM). Therefore, the aim of this study was to investigate the mechanisms of BM cell accumulation, and trafficking to circulating blood and lung tissue after SEA airway exposure. Male BALB/C mice were intranasally exposed to SEA (1µg), and at 4, 12 and 24h thereafter, BM, circulating blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected. Adhesion of BM granulocytes and flow cytometry for MAC-1, LFA1-α and VLA-4 and cytokine and/or chemokine levels were assayed after SEA-airway exposure. Prior exposure to SEA promoted a marked PMN influx to BAL and lung tissue, which was accompanied by increased counts of immature and/or mature neutrophils and eosinophils in BM, along with blood neutrophilia. Airway exposure to SEA enhanced BM neutrophil MAC-1 expression, and adhesion to VCAM-1 and/or ICAM-1-coated plates. Elevated levels of GM-CSF, G-CSF, INF-γ, TNF-α, KC/CXCL-1 and SDF-1α were detected in BM after SEA exposure. SEA exposure increased production of eosinopoietic cytokines (eotaxin and IL-5) and BM eosinophil VLA-4 expression, but it failed to affect eosinophil adhesion to VCAM-1 and ICAM-1. In conclusion, BM neutrophil accumulation after SEA exposure takes place by integrated action of cytokines and/or chemokines, enhancing the adhesive responses of BM neutrophils and its trafficking to lung tissues, leading to acute lung injury. BM eosinophil accumulation in SEA-induced acute lung injury may occur via increased eosinopoietic cytokines and VLA-4 expression.