Granuloma formation and hemopoiesis induced by C36-48-mycolic acid-containing glycolipids from Nocardia rubra

Abstract

As previously reported (I. Yano, I. Tomiyasu, S. Kitabatake, and K. Kaneda, Acta Leprologica 2:341-349, 1984), Nocardwa rubra, one of the nonpathogenic actinomycetes, possesses three classes of mycolic acidcontaining glycolipid, i.e., glucose mycolate, trehalose dimycolate, and trehalose monomycolate. The carbon chain length of their mycolic acids is shorter (C_3&,a) than that in mycobacteria (longer than C70), and the glycolipid consists of only a-mycolic acid. One intravenous administration of 500 ,Ig of each purified glycolipid to ICR mice in the form of water-in-oil-in-water emulsion without any protein antigens caused prominent granuloma formation in the lungs, spleen, and liver. The lung index in the treated mice was about 3.5 times larger than that in the control mice (given water-in-oil-in-water emulsion only) at 1 week after the injection and then rapidly declined, while spleen and liver indices peaked at 2 weeks after the injection and persisted longer. The granuloma consisted of macrophages, some of which phagocytized glycolipid micelles, lymphocytes, monocytes, and neutrophils. In addition, many small hemopoietic islands were observed in the liver sinusoids, where various immature blood cells were trapped by the prominent cytoplasmic projections of Kupffer cells. The granuloma formation and hemopoiesis observed here are considered to be the most characteristic morphological expression of macrophage activation in these organs. This is the first report to show that such histological changes can be induced by chemically defined and homogeneous mycolic acid-containing glycolipids other than those of mycobacteria.

Mycolic Acid‐Containing Glycolipid as a Possible Virulence Factor of Rhodococcus equi for Mice

“…Part of the pathological changes induced by viable bacteria might be ascribed to some factor other than glycolipid of R. equi. Granuloma-forming capacity of glycoplipid from R. equi seems to be comparable to that observed in glycolipid from Nocardia (10). Nocardia species produce various glycolipids containing mycolic acid ranging from C30 to C60, and it is shown that granuloma-forming activity is small if mycolic acid is shorter than C40.…”

Anti‐Cord Factor (Trehalose 6,6′‐Dimycolate) IgG Antibody in Tuberculosis Patients Recognizes Mycolic Acid Subclasses

“…Initially, cord factor was considered to be a potent virulence factor since it had been isolated from the highly virulent M. tuberculosis strain, which grows as a serpentine cord on the surface culture (4). However, it was subsequently found that cord factor and analogous glycolipids exist widely among virulent and avirulent Mycobacterium, Nocardia, Rhodococcus and Corynebacterium (1,22), and furthermore, that they possess various immunostimulatory properties including granuloma-forming activity, adjuvant activity, anti-tumor activity and non-specific infection prevention activity (1,3,16,(26)(27)(28)30). Thus, immunologically, cord factor seems to stimulate cellular immunity (Th 1 response dominant) as an adjuvant and to be non-specific as an antigen.…”

Pathogenesis of Rhodococcus equi infection in mice: Roles of virulence plasmids and granulomagenic activity of bacteria

“…equi produces glycolypids containing different mycolic acid structures ranging widely from C,, to C,, [28,30]. Purified glycolipids of rhodococci and Nocardia rub-a have shown various biological activ- ities, including granuloma formation and hemopoiesis [28,31,32]. Gotoh et al [28] showed that the carbon length of mycolic acid from R. equi is critical in granuloma formation in murine liver.…”