Novel pathophysiological role of classical chemotactic peptide receptors and their communications with chemokine receptors

The bacterial N-formylpeptides, such as N-formyl-Met-Leu-Phe (fMLF), are so me of the first identified and most potent chemoattractants for phagocytic leukocytes. Two fMLF receptors, the high affinity formyl peptide receptor ( FPR) and its low affinity variant FPR-like I (FPRL1), belong to the seven-t ransmembrane, Gi protein-coupled receptor superfamily which also includes c hemokine receptors. Despite their reaction with bacterial chemotactic pepti des, the physiological role of these receptors in humans remains unclear Ou r recent studies have identified novel exogenous as well as host-derived ag onists for FPR and FPRL1. Furthermore, activation of these receptors by the ir agonists results in desensitization of the receptors for other chemoattr actants, including two chemokine receptors, CCR5 and CXCR4, which serve as major co-receptors for HIV-1. These results suggest that FPR and FPRL1 may play important roles not only in host defense and immunological responses b ut also in the fine tuning of cell activation in the presence of multiple s timuli.