Effect of protein source on nitrogen balance and plasma amino acids in exercising horses.

Plasma AA in horses fed either an all-hay or a hay and grain diet in a traditional format have not been investigated. Eight horses were divided into 2 groups: a hay group fed only grass hay or a hay and a grain group (HG) fed in a crossover design for two 5-wk periods. After the first period, horses were fasted overnight, followed by feeding with blood sampling every hour for 6 h. A 4-d total fecal and urine collection to evaluate N balance followed. A 10-d washout period separated the 5-wk feeding periods, during which horses switched diets. The second period was also followed by fasting, feeding, blood sampling, and a 4-d collection period. Horses consumed 840 g of CP in the hay group and 865 g of CP in the HG group. Horses in the hay group had a 2.4 ± 2.4 g/d N balance, which was not different from 0 (P = 0.34), whereas horses in the HG group had 5.4 ± 2.4 g/d N balance, which was different from 0 (P = 0.045). Fecal N excretion was greater for the hay group compared with the HG group (hay = 51.1 ± 1.3 g/d and HG = 45.5 ± 1.3 g/d; P = 0.011), and urine N excretion was greater for the HG group compared with the hay group (hay = 79.3 ± 2.8 g/d and HG = 89.2 ± 2.8 g/d; P = 0.026). Plasma AA concentrations were greater in the HG group compared with the hay group for Met (P = 0.001), Lys (P = 0.001), Ile (P = 0.047), Arg (P < 0.001), Gln (P = 0.009), and Orn (P = 0.002). Plasma concentrations were less for the HG group compared with the hay group for Thr (P < 0.001) and Ala (P < 0.001). Plasma concentrations of urea were greater for the HG group compared with the hay group (P < 0.001), whereas 3-methyl-histidine concentrations were greater for the hay group compared with the HG group (P < 0.001). The effect of diet on the excretion of N via feces vs. urine in the hay and HG groups is typical. The early increases in the plasma concentrations of Met, Val, Ile, Leu, Phe, Lys, Arg, and Ala during the postfeeding phase are most likely due to increased foregut digestibility as well as a greater quality AA profile in the grain. The greater concentrations of Thr, Leu, and Val later in the postfeeding phase for the hay group most likely reflects slower digestion because of prolonged consumption time compared with the HG group. Improved N balance observed in the HG group supports the fact that the HG group had more available AA via the AA profile and foregut digestibility of the HG diet. Despite the fact that both groups consumed similar amounts of CP, the AA profile and availability affected N balance.

Role of passenger leukocytes in allograft rejection: effect of depletion of donor alveolar macrophages on the local production of TNF-alpha, T helper 1/T helper 2 cytokines, IgG subclasses, and pathology in a rat model of lung transplantation.

Acute lung allograft rejection is believed to be initiated by passenger leukocytes, such as alveolar macrophages (AM), in the donor organ, which release TNF-alpha, and present alloantigens to host lymphocytes, to up-regulated Th1 cellular and humoral immunity. However, the role of donor AM in local TNF-alpha synthesis, and their ability to induce local Th1 cellular and humoral immunity have not been evaluated. By depleting Brown Norway (BN, RT1n) rat lung allografts of AM before transplantation into Lewis rat (LEW, RT1(1)) recipients, the current study determined the role of donor AM in including the production of TNF-alpha, IFN-gamma (Th1 cytokine), IL-4 (Th2 cytokine), IgG subtypes, and rejection pathology in the allograft. The data show that compared with untreated BN allografts, pretransplant depletion of donor lung AM resulted in significantly less TNF-alpha, and IFN-gamma production in allograft bronchoalveolar lavage fluid with variable effects on local IL-4 production. Depletion of AM in the donor lung before transplantation affected the local production of several IgG subclasses. However, pretransplant depletion of donor AM had no effect on the development of the pathology of severe acute rejection. These data show that donor AM have a central role in the local synthesis of TNF-alpha and induce the production of IFN-gamma and IgG subtypes, locally, during acute lung allograft rejection. However, depletion of AM before transplantation does not prevent the development of severe acute rejection in BN rat lungs, transplanted into LEW recipients.

Impaired IgG production in the lungs of HIV-infected individuals.

Human immunodeficiency virus (HIV)-infected individuals are at risk for pulmonary infections with encapsulated bacterial pathogens. This could reflect impaired production of opsonizing antibodies in the lower respiratory tract. We examined antibody production in the alveolar space by measuring immunoglobulin concentrations in bronchoalveolar lavage (BAL) of HIV-infected patients and normal volunteers and by assessing the ability of alveolar macrophages (AM) to induce immunoglobulin production in normal peripheral blood mononuclear cells (PBMC). BAL from HIV-infected patients contained significantly less IgG than normal BAL. IgA and IgM concentrations were similar in both groups. Normal AM supported IgG and IgA production in PBMC. While HIV AM could induce IgA production in PBMC, in no instance did they induce IgG secretion. HIV AM produced significantly more transforming growth factor-beta (TGF-beta), a factor known to suppress IgG production, than normal AM. Finally, TGF-beta antibodies blocked the inhibitory effect of HIV AM on normal IgG secretion without affecting IgA secretion. These findings demonstrate impaired production of opsonizing IgG in the alveolar space of HIV-infected subjects and implicate excess TGF-beta production by AM as the cause of this impairment.

Effect of human lung allograft alveolar macrophages on IgG production: immunoregulatory role of interleukin-10, transforming growth factor-beta, and interleukin-6.

Alveolar macrophages (AM) are crucial to initiating and maintaining local immune responses. The increased susceptibility to pulmonary infections in lung allograft recipients may be due to impaired AM function resulting in diminished cellular and humoral immunity. We have previously reported that control AM were potent stimulators of IgG production from allogeneic peripheral blood mononuclear cells (PBM) in a manner that was dependent on gamma-interferon (gamma IFN). The ability of allograft AM to induce IgG production is unknown. The purpose of the current study was to compare the ability of allograft and control AM to induce IgG production from allogeneic PBM. In contrast to control AM which induced a dose-dependent stimulation of IgG production from allogeneic PBM, allograft AM were highly suppressive of IgG production. The inhibition was not due to a lack of allograft AM stimulation of gamma IFN production from responding lymphocytes. Supernatants from allograft AM were highly suppressive of control AM-induced IgG production. Allograft AM produced greater quantities of interleukin (IL-10) than control AM while transforming growth factor-beta (TGF-beta) production from these cells was comparable. Blocking antibodies to IL-10 and TGF-beta reversed the inhibition of IgG production to 63% and 60% of control, respectively. In addition, the production of interleukin 6 (IL-6), a macrophage-derived cytokine crucial to the stimulation of IgG synthesis, was deficient in the allograft AM. Addition of IL-6 to allograft AM and allogeneic PBM co-cultures restored IgG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Allogeneic bronchoalveolar lavage cells induce the histology of acute lung allograft rejection, and deposition of IgG2a in recipient murine lungs.

The immunologic and histologic changes associated with lung allograft rejection are believed to result from the presentation of donor lung alloantigens to recipient lymphocytes resulting in up-regulated Th1 lymphocyte activity. The ability of allogeneic lung immune cells to induce the pathologic and immunologic changes associated with acute lung allograft rejection are unknown. The current study determined whether allogeneic (C57BL/6, I-a(b)) bronchoalveolar lavage (BAL) cells (> or = 97% macrophages), when instilled into the lungs of recipient BALB/c mice (I-a(d)), induced the histology and immunology associated with acute lung allograft rejection. BALB/c mice received BAL cells from either C57BL/6 mice (allogeneic instillate) or BALB/c mice (autologous instillate) or PBS (control) by nasal insufflation weekly for 4 wk. Allogeneic BAL cells resulted in a lymphocytic bronchitis and vasculitis analogous to grade 1 to 2 lung allograft rejection. The mice given allogeneic instillates had a greater percentage of lymphocytes in the BAL fluid than those given autologous instillates. After instillation of allogeneic BAL cells, the Th1 cytokines, IL-2 and IFN-gamma (IFN-gamma), were produced locally in greater quantities and more frequently than Th2 cytokine IL-10. IL-4, another Th2 cytokine, was not detected. The local production of IgG1 and IgG2a, which are dependent on IL-4 and IFN-gamma, respectively, were increased. However, only IgG2a was deposited in the perivascular and peribronchiolar tissues. These data show that installation of allogeneic BAL cells into the airways of recipient mice induced up-regulated Th1 lymphocyte activity and caused the histologic changes associated with lung allograft rejection.