ICAM-3 (CD50) is expressed by human mast cells: Induction of homotypic mast cell aggregation via ICAM-3

Intercellular adhesion molecule-3 (ICAM-3, CD50), an adhesion receptor of t he immunoglobulin superfamily, is suggested to play a key role in adhesive cellular interactions during the initial phase of an immune response. We he re provide evidence that ICAM-3 is abundantly expressed by cells of the hum an mast cell line HMC-1 and, to a lower degree, by purified skin mast cells , as demonstrated by flow-cytometry, ELISA and RT-PCR. ICAM-3 immunoprecipi tated from surface biotinylated HMC-1 cells migrates as a broad band of Mr 124,000 by Western blot analysis. We also demonstrate that monoclonal antibodies directed against ICAM-3 are capable of inducing rapid HMC-1 cell aggregation, the extent of which stron gly depends on the epitope recognized by the mAb applied. Interestingly, al though inhibitable by two of six mAbs against LFA-I, HMC-1 aggregation indu ced via ICAM-3 appears to be mediated by an adhesive pathway independent of LFA-I. Dermal mast cells are also aggregated with anti-ICAM-3 mAbs, a phen omenon which has not been described before for isolated tissue mast cells. However, this process displays slower kinetics, as compared to HMC-1 cells. That anti-ICAM-3 mAbs are able to mediate biological effects is further ill ustrated by their capability to increase stimulation-dependent release of t he pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8 from HMC-1 cell s. Taken together, these results indicate that ICAM-3 is not only expressed by immature and mature human mast cells, but also possesses functional rel evance and may therefore play a significant role in mast cell associated pr ocesses.