Complement Factors C3a and C5a Are Increased in Bronchoalveolar Lavage Fluid after Segmental Allergen Provocation in Subjects with Asthma

Abstract

Allergic asthma is thought to be the result of an inappropriate specific immune response against common environmental antigens. However, studies of animal asthma models have also linked the innate immune system, in particular complement factors C3a and C5, to murine airway hyperresponsiveness. Because the possible role of these anaphylatoxins in patients with asthma is not understood, we tested the hypothesis that C3a and C5a will increase in the bronchoalveolar lavage (BAL) fluid of patients with asthma after segmental allergen provocation. In a group of 15 subjects with mild asthma we found a significant upregulation of C3a and C5a 24 h after allergen challenge compared with baseline values (p < 0.01). In a control group of healthy volunteers the concentrations remained basically unchanged. Furthermore, we found a strong correlation between both anaphylatoxins and the number of eosinophils (p < 0.01) and, to a lesser degree, with the number of neutrophils (p < 0.05) in BAL fluid. These data suggest a contribution of anaphylatoxins C3a and C5a to the pathogenesis in asthma. However, the pathogenic role of these substances in relation to asthma remains to be elucidated, for example, by using anaphylatoxin receptor blockers as a possible new therapeutic principle.

The Central Role of the Alternative Complement Pathway in Human Disease

“…Using C3aR Ϫ/Ϫ mice, though, the C3aR has been shown to play an unexpectedly important role in experimental models of asthma (44). Furthermore, levels of C3a and C5a are elevated in bronchoalveolar lavage fluid from patients with asthma (45). The role of the alternative pathway has been studied recently in a mouse model of airway hyperresponsiveness (46).…”

Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

“…There is substantial evidence that complement pathways are activated in the lungs of individuals with asthma (6)(7)(8). Specifically, it has been shown that C3a and C5a levels are higher in the BAL of individuals with asthma compared with healthy control subjects at baseline (8).…”

“…Similar effects have been shown for C3a. Specifically, several groups have now shown that deficiencies in C3 (21,22) or the C3aR (7,23,24) protect against the development of allergen-driven AHR. Likewise, the AHR induced by exposure to several environmental stimuli, including RSV (11), particulate matter (22), and ozone (9), has been shown to be C3-dependent.…”

Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

“…Increased levels of C3a in the circulation have been found in diseases such as adult respiratory distress syndrome (24), asthma (25), psoriasis, and atopic dermatitis (AD) (26). C3 fragments are also found intralesionally in inflammatory diseases such as psoriasis (27), eczema (28), and asthma (19,29). Recently, C3b deposition was detected in the stratum corneum of the lesions of psoriasis vulgaris, and a cytoplasmic distribution of C3b as well as C3a was observed in the subcorneal to spinous KCs of allergic contact dermatitis, AD, and psoriatic lesional KCs (30).…”