Loop 1 structure of the leishmanial ICAM-L molecule is crucial for parasite binding and infection of host macrophages.

The binding of each intercellular adhesive molecule (ICAM) molecule fragment from Leishmania amazonensis (ICAM-L) to host macrophages was investigated using an indirect immunofluorescent sandwich technique, based on the observation that ICAM-L can block the uptake of L. amazonensis on the macrophage surface and all prepared ICAM-L fragments can react with rabbit anti-ICAM-L antiserum. The ICAM-L fragments lacking the loop 1 (LI) structure failed to bind to macrophages, and the disruption of the LI structure by mercaptoethanol led to the failure of binding. The fragments containing the LI structure functioned similarly to ICAM-L, by temporarily retarding host cell growth and cell cycle progression, and inhibiting the Leishmania infection of host macrophages. These results suggest that LI constitutes the main determinant of the ICAM-L molecule in binding to, and infection of, host macrophages.