leukotriene-b4 and Cryptococcosis

Swarming behavior of neutrophils has been noticed in both sterile injury and infection models and the mechanisms are being unveiled. So far, no in vitro model has been established to study neutrophil swarming to microbes. In the current study, using live-cell imaging, we observed in vitro neutrophil swarming toward Cryptococcus neoformans, a fungal pathogen causing human meningoencephalitis. Complement C3 and CD11b expression are essential for neutrophils to form cell swarms surrounding C. neoformans. Leukotriene B4 (LTB4) was quickly released by neutrophils during their interactions with C. neoformans. Blockade of LTB4 synthesis inhibited the swarming response to C. neoformans. Importantly, blockade of LTB4 synthesis also significantly reduced neutrophil recruitment in the lung vasculature of mice infected intravenously with C. neoformans, demonstrating a critical role of LTB4 in intravascular neutrophil swarming during infection. Together, this is the first report of neutrophil dynamics of swarming toward a microorganism in vitro, mediated by complement and LTB4.

Topics: Animals; Cell Communication; Cell Movement; Cells, Cultured; Complement System Proteins; Cryptococcosis; Cryptococcus neoformans; Leukotriene B4; Mice; Mice, Inbred C57BL; Neutrophil Activation; Neutrophils

In this study we evaluated the release of some mediators of inflammatory reactions such as histamine (H), leukotriene B4 (LTB4), leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in the cerebrospinal fluid (CSF) of 15 patients with acquired immunodeficiency syndrome (AIDS), eight with opportunistic infections of the central nervous system (CNS) and seven without HIV-related neurological pathology, and of 25 HIV-negative control subjects with other neurological diseases. The cerebrospinal LTB4 level was increased in all the AIDS patients (mean 348 pg/ml); the control group revealed normal levels of LTB4 in the CSF (mean 63.2 pg/ml). The PGD2 level in the HIV-positive (mean 264 pg/ml) patients was higher than of the control subjects (mean 50 pg/ml), while low LTC4 levels were found both in the HIV-positive and control groups. We did not find any significant concentration of H in the CSF of either the HIV-positive or the control subjects. These findings may be due to the presence of chronic HIV infection or to the opportunistic infections of the CNS that so often occur in the latest stages of the disease.

Topics: Brain Diseases; Cryptococcosis; Histamine; HIV Seropositivity; Humans; Leukotriene B4; Leukotrienes; Prostaglandin D2; SRS-A; Toxoplasmosis