The classical pathway of interferon-gamma-dependent activation of macrophages by T helper 1 (T(H)1)-type responses is a well-established feature of cellular immunity to infection with intracellular pathogens, such as Mycobacterium tuberculosis and HIV. The concept of an alternative pathway of macrophage activation by the T(H)2-type cytokines interleukin-4 (IL-4) and IL-13 has gained credence in the past decade, to account for a distinctive macrophage phenotype that is consistent with a different role in humoral immunity and repair. In this review, I assess the evidence in favour of alternative macrophage activation in the light of macrophage heterogeneity, and define its limits and relevance to a range of immune and inflammatory conditions.

Alternative activation of macrophages

Endometriosis

Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the advent of the AIDS pandemic, cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality and a frequently life-threatening opportunistic mycosis among patients with AIDS. Both basic and clinical research have accelerated in the 1990s, and this review attempts to highlight some of these advances. The discussion covers recent findings, current concepts, controversies, and unresolved issues related to the ecology and genetics of C. neoformans; the surface structure of the yeast; and the mechanisms of host defense. Regarding cell-mediated immunity, CD4+ T cells are crucial for successful resistance, but CD8+ T cells may also participate significantly in the cytokine-mediated activation of anticryptococcal effector cells. In addition to cell-mediated immunity, monoclonal antibodies to the major capsular polysaccharide, the glucuronoxylomannan, offer some protection in murine models of cryptococcosis. Clinical concepts are presented that relate to the distinctive features of cryptococcosis in patients with AIDS and the diagnosis, treatment, and prevention of cryptococcosis in AIDS patients.

Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans.

Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain.

https://www.fertstert.org/article/S0015-0282(00)01630-7/pdf

Immunobiology of endometriosis

Increased activation of pelvic macrophages in infertile women with mild endometriosis.

Altered maturation and function of peritoneal macrophages: Possible role in pathogenesis of endometriosis

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory infection in infants and young children, but the pathogenesis of RSV-induced inflammation is not well defined. We hypothesized that in vitro infection of a human bronchial epithelial cell line (BEAS) would induce production of proinflammatory cytokines. BEAS cells were infected with RSV, and cells and supernatants were assayed for cytokine mRNA and protein changes at several time points after infection. Cytokine mRNA in BEAS cells was measured by polymerase chain reaction of reverse-transcribed RNA from whole cell lysates; cytokine levels in supernatants were measured by bioassay or immunoassay. Our results indicated that interleukin-5ay or immunoassay. Our results indicated that interleukin-8 (IL-8) was induced at 4 h after infection (during the eclipse phase of RSV infection) with accumulation of IL-8 in supernatants by 24 h after infection. Increased levels of IL-6 and granulocyte macrophage colony-stimulating factor in supernatants were only detected by 96 h after infection, during the RSV replicative phase. Interferon-alpha and -gamma transcripts were not detectable at any time point. We conclude that the effects of RSV on airway inflammation may be at least partly mediated by sequential production of proinflammatory cytokines in infected airway epithelium.

Respiratory syncytial virus-induced cytokine production by a human bronchial epithelial cell line

Accentuated cyclic activation of peritoneal macrophages in patients with endometriosis.

Acute exposure of animals and humans to ozone results in decrements in lung function, development of airway hyperreactivity, inflammation, edema, damage to pulmonary cells, and production of several compounds with tissue damaging, fibrinogenic or fibrotic potential. The contribution of airway epithelial cells and alveolar macrophages to these processes is unclear. In this study we have directly exposed human alveolar macrophages and human airway epithelial cells to ozone in vitro and measured the cytotoxic effects of ozone, as well as the production of the inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), and fibronectin, all of which are substantially elevated in the bronchoalveolar lavage fluid of humans exposed to ozone. Cells were grown on rigid, collagen-impregnated filter supports, and the interaction of cells with ozone facilitated by exposing them to the gas with medium below the support but no medium on top of the cells. The results show that, although macrophages are much more sensitive to ozone than epithelial cells, they do not produce increased amounts of IL-6, IL-8, or fibronectin following ozone exposure. In contrast, epithelial cells produce substantially more of all three proteins following ozone exposure, and both IL-6 and fibronectin are secreted vectorially. An immortalized human airway epithelial cell line (BEAS 2B) was used in these experiments since human airway epithelial cells are infrequently available for in vitro studies. Data from this study extend previous findings which suggest that the BEAS cell line is a useful model to study the interaction between airway epithelial cells and environmental toxicants.

Susanne Becker

Papers

Increased activation of pelvic macrophages in infertile women with mild endometriosis.

Altered maturation and function of peritoneal macrophages: Possible role in pathogenesis of endometriosis

Respiratory syncytial virus-induced cytokine production by a human bronchial epithelial cell line

Accentuated cyclic activation of peritoneal macrophages in patients with endometriosis.

Ozone-induced release of cytokines and fibronectin by alveolar macrophages and airway epithelial cells