Enhanced interleukin-8 release and gene expression in macrophages after exposure to Mycobacterium tuberculosis and its components.

Abstract

Mycobacterium tuberculosis infection is accompanied by acute and chronic inflammatory infiltrates associated with necrotizing granulomas in lung tissue. The cellular infiltrate is characterized by inflammatory cells which include neutrophils, lymphocytes, and macrophages. In animal and in vitro models of mycobacterial infection, cytokines including tumor necrosis factor-c (TNF-a), interferon gamma (IFNy), and interleukin-1lf participate in granulomatous inflammation. We hypothesized that interleukin-8, a potent chemoattractant for neutrophils and lymphocytes, could be released by activated alveolar macrophages after exposure to M. tuberculosis or its components and contribute to granulomatous lung inflammation. A quantitative immunoassay revealed that IL-8 protein release was significantly elevated in supernatants of macrophages and in lavage fluid obtained from patients with pulmonary tuberculosis compared to normal controls. In addition, Northern blots demonstrated striking up-regulation of IL-8 mRNA in macrophages from these patients. M. tuberculosis and its cell wall components lipoarabinomannan (LAM), lipomannan (LM), and phosphoinositolmannoside (PIM) stimulated IL-8 protein release and mRNA expression in vitro from alveolar macrophages, but deacylated LAM did not. Neutralizing antibodies to TNF-a and/or IL-1-a and P blocked 83% of the stimulation. IL-8 synthesis and release is an early response of macrophages after phagocytosis ofM. tuberculosis. Its production serves to attract both acute and chronic inflammatory cells of active infection and thus participates in the process of containment of the pathogen. (J. Clin.

Mycobacterium tuberculosis H37Rv Parietal and Cellular Lipoarabinomannans

“…The Gro spin system defined from the 1 H-31 P HMQC spectrum (H-3/H-3Ј 3.86/3.80 ppm) (Fig. 6b) and from the HO-HAHA spectrum (H-1/H-1Ј at 4.36/4.14 ppm and H-2 at 5.12 ppm) corresponds to a diacylated Gro by reference to the standard 1,2-diacyl-3-phospho-sn-glycerol unit in Me 2 SO-d 6 : ␦ H-1/H-1Ј 4.33/4.13, ␦ H-2 5.10, ␦ H-3/H-3Ј 3.87/3.80.…”

“…7a). In comparison to a standard, a L-␣-lysophosphatidylinositol dissolved in Me 2 SO-d 6 (1-acyl-2-lyso-sn-glycero-3-phospho-(1-D-myo-inositol), ␦ H-1/H-1Ј 3.99/ 3.97, ␦ H-2 3.75, ␦ H3/H3Ј 3.78/3.76), the Gro 1 H chemical shifts (Table II) indicated that the Gro was monoacylated on C1. Moreover, from the chemical shifts of the myo-Ins protons (Table II), the absence of fatty acyl appendage on the myo-Ins unit was deduced.…”

“…They regulate cytokine secretion (3)(4)(5)(6)(7)(8)(9)(10), block the transcriptional activation of interferon-␥ (10), and neutralize the potentially cytotoxic oxygen free radicals (11). Mannosylated LAMs (ManLAMs) selectively bind murine and human macrophages via the mannose receptor (12,13) and have been found to stimulate CD4/CD8 double negative and CD8 ␣␤T cells restricted by CD1 molecules (14).…”

Anti-mycobacterial treatment reduces high plasma levels of CXC-chemokines detected in active tuberculosis by cytometric bead array

“…Tuberculous granulomas consist of macrophages, dendritic cells, T and B cells and fibroblasts surrounding cells infected with the bacteria and thus containing the dissemination and growth of the bacteria in the host. Production of CXCL8 during Mycobacterium tuberculosis infection modulates neutrophil and lymphocyte migration to the granuloma and high levels of CXCL8 have been associated with necrotising granulomas in infected lung tissue (Zhang et al 1995). Other chemokines, such as CXCL9, CXCL10, CCL2 and CCL5, also act in the immune response against TB.…”

Lipoarabinomannans: characterization of the multiacylated forms of the phosphatidyl-myo-inositol anchor by NMR spectroscopy

“…Lipoarabinomannans (LAMs), found ubiquitously in the genus Mycobacterium [2], represent the major antigens modulating immune responses of the host [3,4]. For example, they have been shown to regulate cytokine secretion [5][6][7][8][9][10][11][12], block the transcriptional activation of interferon-γ [13] and neutralize the potentially cytotoxic oxygen free radicals [13]. In addition, mannosylated LAMs (ManLAMs) selectively bind murine and human macrophages via the mannose receptor [14,15].…”