Gingival histoplasmosis: An atypical presentation of African histoplasmosis in three baboons (Papio spp).

Gingival lesions as the sole manifestation of African histoplasmosis (Histoplasma capsulatum var. duboisii) have never been reported in baboons. Grossly, lesions can be indistinguishable from bacterial ulcerative gingivitis or gingival hyperplasia. Clinical outcomes of primary gingival histoplasmosis in baboons are unknown and may complicate colony management decisions.

Leukoreduction of packed red blood cells attenuates proinflammatory properties of storage-derived microvesicles.

BACKGROUND: Leukoreduction prior to packed red blood cell (pRBC) storage is not a universally accepted practice. Our laboratory has previously shown that microvesicles (MVs) accumulate in pRBC units during storage and play an important role in lung injury after resuscitation. Currently, the effect of leukoreduction on MV formation in stored pRBC units is unknown. In the present study, we investigated the hypothesis that leukoreduction of pRBC units prior to storage would attenuate the production of MVs and decrease pulmonary inflammation after hemorrhage and resuscitation. METHODS: Leukoreduced and nonleukoreduced pRBC units were prepared from human donors and C57/Bl6 mice and stored for up to 42 d and 14 d, respectively. At intervals during storage, MVs were isolated from pRBC units, quantified and characterized based on size, morphology, and levels of proinflammatory cytokines. In additional experiments, mice underwent controlled hemorrhage followed by resuscitation with normal saline (NS) with or without equal numbers of MVs isolated from leukoreduced or nonleukoreduced stored mouse pRBC. Histologic lung sections were evaluated for the presence of tissue edema and inflammatory cells. RESULTS: For both human and mouse pRBCs, the number of MVs significantly increased throughout the storage period. There were significantly fewer MVs present in leukoreduced units. The average MV size significantly increased over time and was similar between groups. Levels of interleukin 1α (IL-1α), regulated on activation, normal T cell expressed and secreted (RANTES), and macrophage-derived chemokine (MDC) were lower in MVs from leukoreduced pRBC units as compared with MVs from nonleukoreduced units. Hemorrhaged mice resuscitated with NS with the addition of MV from leukoreduced pRBC demonstrated significantly less pulmonary edema and inflammatory cell recruitment as compared to those resuscitated with NS with the addition of MV from nonleukoreduced pRBC. CONCLUSIONS: Prestorage leukoreduction of pRBC units reduces the formation and proinflammatory properties of MV, which in turn decreases lung injury secondary to MV from stored pRBC units after hemorrhage and resuscitation.

Macrophage-derived chemokine (CCL22) is a novel mediator of lung inflammation following hemorrhage and resuscitation.

Resuscitation of patients after hemorrhage often results in pulmonary inflammation and places them at risk for the development of acute respiratory distress syndrome. Our previous data indicate that macrophage-derived chemokine (MDC/CCL22) is elevated after resuscitation, but its direct role in this inflammatory response is unknown. Macrophage-derived chemokine signaling through the C-C chemokine receptor type 4 (CCR4) is implicated in other pulmonary proinflammatory conditions, leading us to hypothesize that MDC may also play a role in the pathogenesis of lung inflammation following hemorrhage and resuscitation. To test this, C57BL/6 mice underwent pressure-controlled hemorrhage followed by resuscitation with lactated Ringer's solution. Pulmonary inflammation and inflammatory cell recruitment were analyzed with histological staining, and serum- and tissue-level cytokines were measured by enzyme-linked immunosorbent assay. Pulmonary inflammation and cell recruitment following hemorrhage and resuscitation were associated with systemic MDC levels. Inhibition of MDC via injection of a specific neutralizing antibody prior to hemorrhage and resuscitation significantly reduced pulmonary levels of the chemotactic cytokines keratinocyte-derived chemokine and macrophage inflammatory proteins 2 and 1α, as well as inflammatory cell recruitment to the lungs. Intravenous administration of recombinant MDC prior to resuscitation augmented pulmonary inflammation and cell recruitment. Histological evaluation revealed the expression of CCR4 within the bronchial epithelium, and in vitro treatment of activated bronchial epithelial cells with MDC resulted in production and secretion of neutrophil chemokines. The present study identifies MDC as a novel mediator of lung inflammation after hemorrhage and resuscitation. Macrophage-derived chemokine neutralization may provide a therapeutic strategy to mitigate this inflammatory response.