DIFFERENTIAL EXPRESSION OF COMPLEMENT RECEPTORS ON HUMAN BASOPHILS AND MAST-CELLS - EVIDENCE FOR MAST-CELL HETEROGENEITY AND CD88 C5AR EXPRESSION ON SKIN MAST-CELLS/

Complement-dependent activation of immune cells is regulated by cell s urface membrane receptors. In this study, expression of complement rec eptors (CR) on human blood basophils (n = 11), tissue mast cells (lung , n = 7; skin, n = 10; uterus, n = 4; tonsil, n = 3; heart, n = 10), a nd on respective human cell lines (basophil line KU-812, mast cell lin e HMC-1) was analyzed by the use of mAbs and indirect immunofluorescen ce. Normal blood basophils and KU-812 cells were found to express C5aR (CD88), membrane cofactor protein (CD46), decay-accelerating factor ( CD55), and membrane attack complex inhibitory factor (CD59), as well a s the previously recognized CR1 (CD35), CR3 alpha (CD11b), CR4 alpha ( CD11c), and CR3/4 beta (CD18). Mast cells from all organs as well as H MC-1 cells expressed CD46, CD55, and CD59, but not CD11b, CD21, or CD3 5. The C5aR (CD88) was detectable on skin mast cells, a subset (5 to 1 5%) of cardiac mast cells, and on HMC-1 cells, but not on lung, uterus , or tonsillar mast cells (<5%). Moreover, double immunoperoxidase sta ining (tryptase vs C5aR/CD88) revealed in situ expression of C5aR on s kin, but not lung mast cells. Recombinant human (rh) C5a, at 10(-10) t o 10(-7) M, induced secretion of histamine from basophils (rhC5a, 10(- 8) M: 53.4 +/- 3.1% vs control <5%) and from skin mast cells (rhC5a, 1 0(-8) M: 25.8 +/- 16.1% vs control <10% histamine release), but not fr om other mast cells (rhC5a or control: <10%, p > 0.05). The rhC5a-indu ced secretion of histamine from basophils and skin mast cells was inhi bited by S5/1, a blocking Ab against CD88 (basophils: 37.2% to 75.1%; skin mast cells: 39.2% to 83.9% inhibition, p < 0.05). Together, this study shows that a) basophils and mast cells express a different profi le of complement receptors, b) C5a-dependent mediator release in skin mast cells and basophils is mediated via CD88, and c) mast cells const itute a heterogenous lineage in terms of expression of the C5a binding site CD88.