BLOOD-DERIVED AND SKIN-DERIVED MONOCYTES MACROPHAGES RESPOND TO C3A BUT NOT TO C3A(DESARG) WITH A TRANSIENT RELEASE OF CALCIUM VIA A PERTUSSIS-TOXIN-SENSITIVE SIGNAL-TRANSDUCTION PATHWAY/
J. Zwirner et al., BLOOD-DERIVED AND SKIN-DERIVED MONOCYTES MACROPHAGES RESPOND TO C3A BUT NOT TO C3A(DESARG) WITH A TRANSIENT RELEASE OF CALCIUM VIA A PERTUSSIS-TOXIN-SENSITIVE SIGNAL-TRANSDUCTION PATHWAY/, European Journal of Immunology, 27(9), 1997, pp. 2317-2322
Controversial results have been published in the past regarding the fu
nctional reactivity of monocytes (Mo) and macrophages (M Phi) to the a
naphylatoxin C3a and its degradation product C3a(desArg). in this stud
y we performed binding and calcium mobilization experiments with recom
binant human C3a (rC3a) and rC3a(desArg). Blood Mo displayed non-inhib
itable binding of FITC-labeled rC3a (rC3a(FITC)) but responded to rC3a
with a transient release of the intracellular calcium concentration (
[Ca2+](i)), whereas rC3a(desArg) was completely inactive. In contrast,
binding of rC3a(FITC) to eosinophilic granulocytes and the mast cell
line HMC-1 which have been shown previously to express C3a binding sit
es could be blocked by a monoclonal anti-C3a antibody. The rC3a-induce
d [Ca2+](i) release in blood Mo was pertussis toxin (PTX)-sensitive su
ggesting the involvement of G-proteins in the signal transduction path
way. Skin-derived Mo/M Phi reacted similarly to blood Mo as no specifi
c binding of rC3a(FITC) to these cells could be demonstrated, whereas
an intracellular release of calcium ions in response to the anaphylato
xin was observed. Homologous desensitization to rC3a but not heterolog
ous desensitization to rC5a was detected in further experiments. The f
unctional effect of C3a, but not the unspecific binding of rC3a(FITC)
to blood Mo and skin-derived Mo/M Phi could be blocked by the monoclon
al anti-C3a antibody. These results suggest the expression of the rece
ntly cloned G-protein-coupled receptor for C3a on human blood Mo and s
kin-derived Mo/M Phi. However, the total number of specific C3a bindin
g sites on these cells is distinctly lower as compared to eosinophilic
granulocytes and cells of the mast cell line HMC-1. The small number
of C3a receptors on Mo/M Phi may be masked by a pronounced non-inhibit
able binding of rC3a(FITC). This binding, however, may contribute to t
he recently described biological effects of C3a(desArg) on Mo.