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, the authors 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. The authors were 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.