Characterization of protective mucosal and systemic immune responses elicited by pneumococcal surface protein PspA and PspC nasal vaccines against a respiratory pneumococcal challenge in mice.

Pneumococcal surface protein A (PspA) and PspC are virulence factors that are involved in the adhesion of Streptococcus pneumoniae to epithelial cells and/or evasion from the immune system. Here, the immune responses induced by mucosal vaccines composed of both antigens as recombinant proteins or delivered by Lactobacillus casei were evaluated. None of the PspC vaccines protected mice against an invasive challenge with pneumococcal strain ATCC 6303. On the other hand, protection was observed for immunization with vaccines composed of PspA from clade 5 (PspA5 or L. casei expressing PspA5) through the intranasal route. The protective response was distinguished by a Th1 profile with high levels of immunoglobulin G2a production, efficient complement deposition, release of proinflammatory cytokines, and infiltration of neutrophils. Intranasal immunization with PspA5 elicited the highest level of protection, characterized by increased levels of secretion of interleukin-17 and gamma interferon by lung and spleen cells, respectively, and low levels of tumor necrosis factor alpha in the respiratory tract.

In vivo hydroquinone exposure impairs allergic lung inflammation in rats.

Hydroquinone (HQ) is naturally found in the diet, drugs, as an environmental contaminant and endogenously generated after benzene exposure. Considering that HQ alters the immune system and its several source of exposures in the environment, we hypothesized that prolonged exposure of HQ could affect the course of an immune-mediated inflammatory response. For this purpose, male Wistar rats were intraperitoneally exposed to vehicle or HQ once a day, for 22 days with a 2-day interval every 5 days. On day 10 after exposure with vehicle or HQ, animals were ovalbumin (OA)-sensitized and OA-aerosolized challenged on day 23. HQ exposure did not alter the number of circulating leukocytes but impaired allergic inflammation, evidenced by lower number of leukocytes in the bronchoalveolar lavage fluid 24h after OA-challenge. Reduced force contraction of ex vivo tracheal segments upon OA-challenge and impaired mesentery mast cell degranulation after in situ OA-challenge were also detected in tissues from HQ exposed animals. The OA-specificity on the decreased responses was corroborated by normal trachea contraction and mast cell degranulation in response to compound 48/80. In fact, lower levels of circulating OA-anaphylactic antibodies were found in HQ exposed rats, as assessed by passive cutaneous anaphylaxis assay. The reduced level of OA-anaphylactic antibody was not dependent on lower number or proliferation of lymphocytes. Nevertheless, lower expression of the co-stimulatory molecules CD6 and CD45R on OA-activated lymphocytes from HQ exposed rats indicate the interference of HQ exposure with signaling of the humoral response during allergic inflammation. Together, these data indicate specific effects of HQ exposure manifested during an immune host defense.

Chronic blockade of nitric oxide biosynthesis in rats: effect on leukocyte endothelial interaction and on leukocyte recruitment.

INTRODUCTION: Previous studies showed that animals chronically treated with NG-nitro-L-arginine methyl ester (L-NAME) have a reduced inflammatory reaction. Now the role of L-NAME treatment (20 mg/Kg/day/14 days) on leukocyte mobilisation was assessed in rats. METHODS: In vivo leukocyte recruitment evoked by Bothrops jararaca venom (BjV) and nitrite/nitrate (NO2-/NO3-; Griess reaction) were evaluated in the air pouch cavity. Haematological parameters were evaluated in the bone marrow and in the peripheral compartment. Microcirculatory blood flow, number of rolling and adhered leukocytes, vascular reactivity and mast cell activity were studied by intravital microscopy. Blood pressure was measured by the tail-cuff method. L-selectin and beta(2) integrin expressions on peripheral and bone marrow leukocytes were quantified by flow cytometry. RESULTS: When compared with control rats (D-NAME) L-NAME treated rats had reduced PMN cell infiltrate (50%) and NO2-/NO3- (27%) in the air pouch cavity. Rolling leukocytes were decreased (70%) in L-NAME-treated animals, which was reversed by topical application of NO donor (SIN-1). BjV stimulation increased the number of rolling and adhered leukocytes only in control rats. Systemic blood pressure, microcirculatory blood flow and microvascular reactivity was not altered by the treatment. Only the vessel response to acetylcholine was delayed in treated rats. Peripheral PMN cells were increased by L-NAME treatment (100%), but the number of bone marrow cells was not altered. The treatment reduced L-selectin expression on circulating leukocytes, by either with (16%) or without (26%) stimulation with BjV; PMN cells were more affected (32-37%). Impairment of L-selectin expression was also verified in bone marrow cells under stimulation with BjV. CONCLUSIONS: Results show that this schedule of L-NAME treatment promotes a decrease on L-selectin expression. This effect may promote the standstill of leukocytes in the blood compartment and may be responsible, at least in part, for the observed deficient leukocyte-endothelium interactions with subsequent impairment of leukocyte migration to the inflammatory site.