Abstract
The mechanism by which human C5a anaphylatoxin augments the primary humoral response of murine splenocytes to antigen has been investigated. Culture supernatants were generated from splenic adherent cells or macrophage cell lines after exposure to a brief pulse of human C5a. Supernatants from the macrophage-like cell line P388D1, which bears surface receptors for C5a, enhance the PFC response to antigen, whereas those from the closely related cell line P388, which lacks surface receptors for C5a, fail to cause enhancement. Supernatants from splenic adherent cells, which also bear C5a receptors, similarly augment the SRBC response. Active supernatants, but not those devoid of activity, were shown to contain interleukin 1 (IL-1) activity by both the thymocyte mitogenesis and thymocyte costimulator assays. None of the supernatants contained IL-2 activity. These observations suggest that the recently described role of human C5a as an immunopotentiating modulator is mediated by its ability to induce production of IL-1 upon binding to specific receptors at the macrophage cell surface.
Highlights
MethodsBALB/c and C3H/St male mice, 5-12 wk of age (from Scripps Clinic and Research Foundation) and CBA/CaJ and B6D2Fa male mice, 8 12 wk of age
We have recently demonstrated the existence of specific receptors on murine macrophages for purified human C5a anaphylatoxin, a low molecular weight glycopeptide released from C5 during complement activation
Human C5a anaphylatoxin binds to specific receptors found predominantly on Iamurine macrophages [11]
Summary
BALB/c and C3H/St male mice, 5-12 wk of age (from Scripps Clinic and Research Foundation) and CBA/CaJ and B6D2Fa male mice, 8 12 wk of age :~Recipient of ResearchCareer DevelopmentAwardAI00374and grant AI15284fromthe U. § Supported in part by Grant-in Aid 79-863from the American Heart Association Dr Chenowethcompletedthis study as an Established Investigatorof the American Heart Association
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