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The role of complement in human immediate hypersensitivity: evidence against involvement of the alternate pathway of complement activation.


 A role for the alternate pathway of complement activation in immediate hypersensitivity reactions was investigated following a number of recent observations which suggested this possibility. The ability of normal human serum to enhance allergen-mediated histamine release from the leukocytes of atopic human donors was not reduced by heating serum to 100°C, nor did the addition of purified C3 to allergen-challenged leukocytes change the percentage of histamine released. To ascertain if cell-bound C3 was involved, we incubated leukocytes with anti-C3: no histamine was released by a preparation of anti-C3 which had been made with a highly purified C3 antigen, nor did preincubation of leukocytes in this anti-C3 inhibit the subsequent allergen-mediated release of histamine. Moreover, most of the anti-C3 antibodies could be recovered in the supernatant at the end of the incubation period. We have been able to confirm previous reports that some anti-C3 preparations can cause the release of histamine and/or can inhibit allergen-mediated release of histamine from human leukocytes. However, further investigation suggested that these latter results were obtained with preparations of anti-C3 contaminated with antibodies against human light chains. Anti-light chain antibodies would be capable of releasing histamine directly from leukocytes or of “desensitizing” leukocytes to subsequent allergen-challenge.
 It is concluded that the release of histamine from human leukocytes challenged by allergens is independent of free or cell-bound C3, and that there is little evidence that the alternate pathway of complement activation is involved in this type of response.