The role of the macrophage in asthma

Abstract

Aeeumulating evidence implicates eells ofthe mononuclear phagocyte lineage in the pathogenesis of bronchial asthma. The evidence for involvement of peripheral blood monoeytes (PBM) and alveolar macrophages (AM) in the pathogenesis of asthma stems from functional studies on peripheral blood monocytes and analysis of the fluid and cellular phases of bronchoalveolar lavage (BAE) samples, and, more recently, from histologic material obtained from endobronchial biopsy in vivo. -• Peripheral blood monocytesIn 1975, Capron etal. produced evidence of IgE receptors on macrophages by showing the role of IgE antibodies in macrophage-dependent cytotoxic damage to parasites (12). This receptor is similar, if not identical, to the Fc,.r found on T and B cells and is referred to as FC.TJ, as it differs in both structure and function from the Fc,.r, found on mast cells and basophils (77). The most important functional difference is that the Fc,,r2 on macrophages is of a lower afiinity (i.e., an estimated dissociation constant for monomeric IgE binding to macrophages and U937 cells of 10|.iM) and is preferentially activated by immune complexes (40). Approximately 5-10% of PBM and AM bear Fc^r, (56,77). This percentage rises to 20% in mildly atopic asthmatic subjects and can be downregulated by eortieosteroid treatment (58).PBM from asthmatic subjeets have enhaneed complement receptor expression (CRE) in the presence or absence of casein, as compared with normal controls (42). Furthermore, the numbers of PBM that form rosettes with eomplenicnt-coated sheep erythroeytes are increased in asthmatic subjects after allergen bronchoprovocation, but not after histamine-induced bronchoconstriction (13). In asthmatic subjeets who respond to corticosteroids (corticosteroid-sensitive (CS) asthmatic subjects), these levels revert to normal after 7 days' treatment with prednisolone, whereas in patients who fail to improve clinically with corticosteroids (corticosteroid-resistant (CR) asthmatic subjects), these levels remain elevated (42). In addition, it has been shown that in vitro colony formation in soft agar by PHA-stimulated mononuelear cells is inhibited by methylprednisolone in CS subjects, but not in CR subjects. The origin of this in vitro resistance was found to be monocyte-derived, rather than lymphocyte-derived (67). We have shown that the expression of the activation antigens CR-1, CR-3, and class II molecules on cultured PBM is elevated in asthmatic subjects, as compared with normal eontrol subjects (89). Furthermore, this enhanced receptor expression is suppressed by hydroeortisone 201 Lane et al.in CS, but not in CR, asthmatic subjects, suggesting ongoing PBM activation in the presence of corticosteroids. Interactions between monocytes and granulocytesActivated PBM generate a number of proinflammatory molecules which can influence the activity of other cell types. For instance, supernatants from activated PBM modulate arachidonic acid metabolism by the cyclooxygenase and lipoxygenase pathway in maerophages, fibroblasts, and gr...

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“…Moreover, alveolar macrophages (AMs) are the most abundant cells in not only the alveoli and distal air space but also conducting airways [16]. These AMs are activated in asthma [17], and may participate in inflammatory events such as the release of cytokines, chemokines, arachidonic acid metabolites, and products of activated O 2 -, which are associated with allergic disease of the lower airways, by direct interaction with T lymphocytes [18][19][20][21].…”

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